Granted Patent
B2
US 12,213,468 · App. 17/004,698 · Granted Feb 4, 2025
Population control using engineered translocations
Assignee:
California Institute of Technology
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Abstract
Embodiments provided herein relate to systems for synthetically-engineered reciprocal chromosomal translocation for gene insertion into a population of organisms such as insects.
Claims (57)
1. A method of distributing one or more genes of interest into a population of insects, the method comprising:
i) providing an insect population, wherein one or more individuals in the insect population comprises a translocation mediated gene drive system; and
ii) inducing a chromosomal translocation in the one or more individuals in the insect population,
wherein the chromosomal translocation generates a translocation-bearing altered insect population, wherein the translocation-bearing altered insect population comprises translocation-bearing individuals that are translocation heterozygotes and translocation-bearing individuals that are translocation homozygotes for the chromosomal translocation and wherein the translocation mediated gene drive system comprises:
a first construct, configured to be positionable at a first insertion site in a first chromosome, wherein the first construct comprises:
a) a first location to insert a first gene of interest;
b) a first promoter;
c) a first fragment of foreign stuffer DNA;
d) a second fragment of foreign stuffer DNA;
e) a first target site of a pair of target sites for an endonuclease positioned between the first and second fragments of foreign stuffer DNA;
f) a first splice acceptor site, positioned downstream from a-e; and
g) a first splice donor site, positioned between b and c, and a second construct, configured to be positionable at a second insertion site in a second chromosome, wherein the second construct comprises:
h) a second location to insert a second gene of interest;
i) a second promoter;
j) a third fragment of foreign stuffer DNA, wherein the third fragment is homologous to the second fragment;
k) a fourth fragment of foreign stuffer DNA, wherein the fourth fragment is homologous to the first fragment;
l) a second target site of the pair of target sites for an endonuclease positioned between the third and fourth fragments of foreign stuffer DNA;
m) a second splice acceptor site, positioned downstream from h- 1 , and
n) a second splice donor site, positioned between i and j, wherein the first and second chromosomes are non-homologous chromosomes,
wherein the first fragment of foreign stuffer DNA is homologous to the fourth fragment of foreign stuffer DNA and the second fragment of foreign stuffer DNA is homologous to the third fragment of foreign stuffer DNA,
wherein a double stranded break created at the first, and second target sites of the pair of target sites allows for homologous recombination between the first and fourth fragments, and between the second and third fragments upon a repair of the double stranded break (DSB),
wherein the repair of the DSB induces a chromosomal translocation and generates a first translocation chromosome and a second translocation chromosome.
2. The method of claim 1 , wherein one or more genes of interest in the translocation-bearing altered insect population encodes for a disease prevention protein/disease refractory protein, or a gene conferring conditional lethality, inability to undergo diapause, sterility, inability to fly.
3. The method of claim 1 , wherein the high frequency is defined as when translocation-bearing versions of chromosomes make up 90% or greater of the total chromosomes in a population as compared to wild type versions of the chromosomes involved in generating the translocation.
4. The method of claim 3 , wherein the rapid rate is defined as replacement of at least 90% of the wild type population chromosomes by the translocation-bearing altered insect population (translocation) after at most 5 generations.
5. The method of claim 1 , wherein the translocation-bearing altered insect population replaces 90% of the target wild type population after 30 generations.
6. The method of claim 1 , wherein the insect is a mosquito.
7. The method of claim 1 , wherein the condition in which translocation-based drive occurs comprises one or more of a population cage, a field cage, or an open environment.
8. The method of claim 1 , wherein the chromosomal translocation spreads to a high frequency within the wild population.
9. The method of claim 1 , wherein the translocation-bearing altered insect population is capable of replacing the wild type population at a rapid rate.
10. The method of claim 1 , wherein the insect is a psyllid.
11. A population of translocation bearing insects comprising a gene drive system comprising:
a first construct, configured to be positionable at a first insertion site in a first chromosome, wherein the first construct comprises:
a) a first location to insert a first gene of interest;
b) a first promoter;
c) a first fragment of foreign stuffer DNA;
d) a second fragment of foreign stuffer DNA;
e) a first target site of a pair of target sites for an endonuclease positioned between the first and second fragments of foreign stuffer DNA;
f) a first splice acceptor site, positioned downstream from a-e; and
g) a first splice donor site, positioned between b and c, and a second construct, configured to be positionable at a second insertion site in a second chromosome, wherein the second construct comprises:
h) a second location to insert a second gene of interest;
i) a second promoter;
j) a third fragment of foreign stuffer DNA, wherein the third fragment is homologous to the second fragment;
k) a fourth fragment of foreign stuffer DNA, wherein the fourth fragment is homologous to the first fragment;
l) a second target site of the pair of target sites for an endonuclease positioned between the third and fourth fragments of foreign stuffer DNA;
m) a second splice acceptor site, positioned downstream from h- 1 , and
n) a second splice donor site, positioned between i and j, wherein the first and second chromosomes are non-homologous chromosomes,
wherein the first fragment of foreign stuffer DNA is homologous to the fourth fragment of foreign stuffer DNA and the second fragment of foreign stuffer DNA is homologous to the third fragment of foreign stuffer DNA,
wherein a double stranded break created at the first, and second target sites of the pair of target sites allows for homologous recombination between the first and fourth fragments, and between the second and third fragments upon a repair of the double stranded break (DSB),
wherein the repair of the DSB induces a chromosomal translocation and generates a first translocation chromosome and a second translocation chromosome.
12. The population of translocation bearing insects of claim 11 , wherein the insects are mosquitos.
13. The population of translocation bearing insects of claim 11 , wherein the insects are psyllids.
14. The method of claim 1 , wherein the translocation-bearing individuals display a fitness that is greater than that of wildtype individuals when challenged in a condition in which a translocation-based drive occurs,
wherein the fitness is defined as a population genetic behavior, over multiple generations, of translocation chromosomes in populations comprising both translocation-bearing individuals and non-translocation-bearing individuals,
wherein the chromosomal translocation is defined as having a higher fitness than wildtype under conditions that result in translocation-bearing chromosomes increasing in frequency over multiple generations,
wherein the translocation is defined as having a lower fitness than wildtype under conditions that result in translocation-bearing chromosomes decreasing in frequency over multiple generations, and
wherein fitness is frequency dependent such that a higher frequency of a first genotype results in an increase in relative fitness of the first genotype with respect to alternative genotypes.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 19, 2024
From: HAY, BRUCE A.; AKBARI, OMAR S.; BUCHMAN, ANNA B.
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 069638/0138 →
Continuity (3)
Provisional Application
62166281
· May 26, 2015
References Cited (400)
US 4676981A
· Silversides et al.
· 1987
[cited by applicant]
US 4879112A
· Silversides et al.
· 1989
[cited by applicant]
US 4946778A
· Ladner et al.
· 1990
[cited by applicant]
US 4980286A
· Morgan et al.
· 1990
[cited by applicant]
US 5139941A
· Muzyczka et al.
· 1992
[cited by applicant]
US 5173414A
· Lebkowski et al.
· 1992
[cited by applicant]
US 5354678A
· Lebkowski et al.
· 1994
[cited by applicant]
US 5436146A
· Shenk et al.
· 1995
[cited by applicant]
US 5474935A
· Chatterjee et al.
· 1995
[cited by applicant]
US 5478745A
· Samulski et al.
· 1995
[cited by applicant]
US 5580859A
· Felgner et al.
· 1996
[cited by applicant]
US 5589377A
· Lebkowski et al.
· 1996
[cited by applicant]
US 5589466A
· Felgner et al.
· 1996
[cited by applicant]
US 5593972A
· Weiner et al.
· 1997
[cited by applicant]
US 5641870A
· Rinderknecht et al.
· 1997
[cited by applicant]
US 5652224A
· Wilson et al.
· 1997
[cited by applicant]
US 5753434A
· Ryner et al.
· 1998
[cited by applicant]
US 5801030A
· McVey et al.
· 1998
[cited by applicant]
US 6013770A
· Reeves et al.
· 2000
[cited by applicant]
US 6284733B1
· Meloen et al.
· 2001
[cited by applicant]
US 7339031B2
· Baker et al.
· 2008
[cited by applicant]
US 7731939B2
· Miller et al.
· 2010
[cited by applicant]
US 20030213005A1
· Alphey et al.
· 2003
[cited by applicant]
US 20050032171A1
· Saxena et al.
· 2005
[cited by applicant]
US 20090183269A1
· Alphey
· 2009
[cited by applicant]
US 20100233249A1
· Sutovsky et al.
· 2010
[cited by applicant]
US 20140283155A1
· Akbari et al.
· 2014
[cited by applicant]
US 20150237838A1
· Hay et al.
· 2015
[cited by applicant]
US 20160060358A1
· Hay
· 2016
[cited by applicant]
US 20190241879A1
· Esvelt et al.
· 2019
[cited by applicant]
JP 63126482A
· 1988
[cited by applicant]
JP 2544120B2
· 1996
[cited by applicant]
KR 1020170041640A
· 2017
[cited by applicant]
WO WO9011092A1
· 1990
[cited by applicant]
WO WO9206180A1
· 1992
[cited by applicant]
WO WO9220316A2
· 1992
[cited by applicant]
WO WO9222635A1
· 1992
[cited by applicant]
WO WO9314188A1
· 1993
[cited by applicant]
WO WO9320221A1
· 1993
[cited by applicant]
WO WO9408598A1
· 1994
[cited by applicant]
WO WO9412649A2
· 1994
[cited by applicant]
WO WO1999065520A1
· 1999
[cited by applicant]
WO WO2001007083A1
· 2001
[cited by applicant]
WO WO2005095458A1
· 2005
[cited by applicant]
WO WO2008009960A2
· 2008
[cited by applicant]
WO WO2010049777A1
· 2010
[cited by applicant]
WO WO2012143401A1
· 2012
[cited by applicant]
WO 2013176772A1
· 2013
[cited by applicant]
WO WO2013176722
· 2013
[cited by applicant]
WO WO2014052693A2
· 2014
[cited by applicant]
WO WO2014096428A1
· 2014
[cited by examiner]
WO WO2014120975A8
· 2014
[cited by applicant]
WO WO2016049230A1
· 2016
[cited by applicant]
WO WO2018049287A2
· 2018
[cited by applicant]
WO WO2018204722A1
· 2018
[cited by applicant]
Biswajit, P., megaTAL-mediate Gene Editing at the CCR5 locus, PhD Dissertation, University of Washington, pp. 1-113, 2016.
[cited by applicant]
Buchman et al., Synthetically engineered Medea gene drive system in the worldwide crop pest
[cited by applicant]
Centers for Disease Control and Prevention (2014). About malaria. Retrieved Apr. 30, 2014, from cdc.gov/malaria/about/facts.html.
[cited by applicant]
Centers for Disease Control and Prevention (2012). Dengue fact sheet. Retrieved Apr. 30, 2014, from cdc.gov/Dengue/faqFacts/fact.html.
[cited by applicant]
Gloor et al., Targeted Gene Replacement in Drosophiloa via P. Element-induced Gap Repair, Science, vol. 253, No. 5024, pp. 1110-1117, 1991.
[cited by applicant]
Gould, F., et al., “Pest Management by Genetic Addiction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, No. 13, pp. 5849-5851, 2019.
[cited by applicant]
Greisman et al., “A general Stategy for Selecting High-Affinity Zinc Finger Proteins for Diverse DNA Target Sites,” 1997, Science, vol. 275:657-661.
[cited by applicant]
Guilinger et al., “Fusion of catalytically inactive Cas9 to Fokl nuclease improves the specificity of genome modification,” Jun. 2014, Nature iotehcnology, vol. 32, No. 6, pp. 577-589.
[cited by applicant]
Hammond et al., The creation and selection ofm utations resistant to a gene drive over multiple generations in the malaria mosquito, PLOS Genetics, vol. 13(10), pp. 1-16, 2017.
[cited by applicant]
Hamza et al., Complementation of Yeast Genes With Human Genes as an Experimental Platform for Functional Testing or Human Genetic Variants, genetics, vol. 201, pp. 1263-1274, 2015.
[cited by applicant]
Hu et al., A Large Gene Family in Fission Yeast Encodes Spore Killers That Subvert Mendel's Law, 2017, eLife, pp. 1-19.
[cited by applicant]
Jinek et al., Structures of Cas9 Endonucleases Reeal RNA-Mediated Conformational Activation, Science, vol. 343, 1247997, 2014, 13 pgs.
[cited by applicant]
Knott et al., crispr-Cas guide the uture of genetic engineering, Science, vol. 631:866-869, 2018.
[cited by applicant]
Naveira et al., The Theoretical Distribution of Lengths of Intact Chromosome Segments Around a Locus Held Heterozygous Witht Backcrossing in a Diploid Species, Genetics, vol. 130:205-209, 1992.
[cited by applicant]
Ngo et al., Computational Complexity Protein Structure Prediction, and the Levinthal Paradox, The Protein Folding and Tertiary Structure Protein, 1994.
[cited by applicant]
Nishimasu et al., Crystal Strucutre of Cas9 in Complex with Guide RNA and Target DNA Cell 156(5), 935-949, 2014.
[cited by applicant]
Notice of Allowance Dated Feb. 3, 2021 in U.S. Appl. No. 15/164,452.
[cited by applicant]
Nowak, C.M,, et al., “Guide RNA Engineering for Versatile Cas9 Functionality,” Nucleic Acids Research, vol. 44, No. 20, pp. 9555-9564, 2016.
[cited by applicant]
Oberhofer, G., et al., Cleave and Rescue, a Novel Selfish Genetic Element and General Strategy for Gene Drive, Supplementary Information for Proceedings of the National Academy of Sciences of the United States of Americ…
[cited by applicant]
Oberhofer, G., et al., Gene Drive and Resilience Through Renewal With Next Generation Cleave and Rescue Selfish Genetic Elements, Proceedings of the National Academy of Sciences of the United States of America, vol. 117…
[cited by applicant]
Office Action dated Mar. 22, 2019 in U.S. Appl. No. 15/164,452.
[cited by applicant]
Office Action Dated Aug. 16, 2018 in U.S. Appl. No. 15/164,452.
[cited by applicant]
Office Action dated Feb. 21, 2020 in U.S. Appl. No. 15/970,728.
[cited by applicant]
Office Action dated Oct. 1, 2020 in U.S. Appl. No. 15/970,728.
[cited by applicant]
Peng, J., et al., High-throughput screens in mammalian cells using the CRISPR-Cas9 system, The FEBS Journal, vol. 282, pp. 2089-2096, 2015.
[cited by applicant]
Reeves, R. G., J. Bryk, P. M. Altrock, J. A. Denton, and F. A. Reed. 2014. “First Steps towards Underdominant Genetic Transformation of Insect Populations.” PloS One 9 (5): e97557.
[cited by applicant]
Restriction Requirement Dated Jan. 11, 2018 in U.S. Appl. No. 15/164,452.
[cited by applicant]
Rudinger, et al., Peptide Hormones, Parsons, (ed.), 1976 University Park Press, Baltimore, MD, pp. 1-7.
[cited by applicant]
Sternberg et al., DNA interrogation by the CRISPR RNA-guided endonuclease Cas9, Nature, vol. 507, (7490), 62-67, 17 pgs., 2014.
[cited by applicant]
Tan et al., “Zinc-finger protein-targeted gene regulatio: Genomewide single-gene specificity,” 2003, PNAS, vol. 100, No. 21, pp. 11997-12002.
[cited by applicant]
Tham et al., Mismatch Repair and Homoeologous Recombination, DNA Repair, vol. 38, pp. 75-83, 2016.
[cited by applicant]
Windbichler, N., P. A. Papathanos, and A. Crisanti. 2008. “Targeting the X Chromosome during Spermatogenesis Induces Y Chromosome Transmission Ratio Distortion and Early Dominant Embryo Lethality in Anopheles Gambiae.” …
[cited by applicant]
Windbichler, Nikolai, Philippos Aris Papathanos, Flaminia Catteruccia, Hilary Ranson, Austin Burt, and Andrea Crisanti. 2007. “Homing Endonuclease Mediated Gene Targeting in Anopheles Gambiae Cells and Embryos.” Nucleic…
[cited by applicant]
World Health Organization (2014b). Dengue factsheet. Retrieved Apr. 30, 2014, from who.int/mediacentre/factsheets/fs117/en/index.html.
[cited by applicant]
Hu et al., A Large Gene Family in Fission Yeast Encodes Spore Killers That Subvert Mendel's Law, 2017.
[cited by applicant]
Alphey, L. Genetic Control of Mosquitoes. Annual Review of Entomology, vol. 59, pp. 205-224, 2014.
[cited by applicant]
Amin et al., Organization of the
[cited by applicant]
Ant et al., Control of the olive fruit fly using genetics-enhanced sterile insect technique, BMC Biology vol. 10, No. 51, 2012.
[cited by applicant]
Baker et al., Genetic sexing for a mosquito sterile-male release, The Journal of Heredity, vol. 7, No. 2, pp. 216-218, 1981.
[cited by applicant]
Beaghton, A., et al., Gene Drive through a Landscape: Reaction-Diffusion Models of Population Suppression and Elimination by a Sex Ratio Distorter, Theoretical Population Biology, vol. 108, pp. 51-69, 2016.
[cited by applicant]
Beaghton, A., et al., Requirements for Driving Antipathogen Effector Genes into Populations of Disease Vectors by Homing, Genetics, vol. 205, No. 4, pp. 1587-1596, 2017.
[cited by applicant]
Ben-David, E. et al., A Maternal-Effect Selfish Genetic Element in Caenorhabditis Elegans, Science vol. 356, No. 6342, pp. 1051-1055, 2017.
[cited by applicant]
Bischof, J. et al., An Optimized Transgenesis System for
[cited by applicant]
Boerjan et al., Lignin biosynthesis, Annual Review of Plant Biology, vol. 54, pp. 519-546, 2003.
[cited by applicant]
Bossin et al., Somatic transformation efficiencies and expression patterns using the JcDNV and piggyBac transposon gene factors in insects, Insect Molecular Biology, vol. 16, pp. 37-47, 2007.
[cited by applicant]
Brelesfoard, et al., Wolbachia-based strategies to control insect pests and disease vectors. Asia-Pacific Journal of Molecular Biology and Biotechnology, vol. 17, pp. 55-63, 2009.
[cited by applicant]
Brunel et al., Cloning and sequencing of pseudomonas genes encoding vanillate demethylase, Journal of Bacteriology, vol. 170, pp. 4924-4930, 1988.
[cited by applicant]
Buchman, A., et al., Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in
[cited by applicant]
Burt, A. et al., Homing Endonuclease Genes: The Rise and Fall and Rise Again of a Selfish Element. Current Opinion in Genetics and Development, vol. 14, pp. 609-615, 2004.
[cited by applicant]
Burt, A. et al Genetic Conflicts in Genomic Imprinting, Proceedings. Biological Sciences/ the Royal Society, vol. 265, No. 1413, pp. 2393-2397, 1998.
[cited by applicant]
Burt, A., Site-Specific Selfish Genes as Tools for the Control and Genetic Engineering of Natural Populations, Proceedings. Biological Sciences/ the Royal Society, vol. 270, No. 1518, pp., 921-28, 2003.
[cited by applicant]
Bushland et al., Eradication of Screw-Worms through Release of Sterilized Males, Science, vol. 122, No. 3163, pp. 287-288, 1955.
[cited by applicant]
Carvalho et al., Mass Production of Genetically Modified Aedes aegypti for Field Releases in Brazil, Journal of Visualized Experiments, vol. 83, e3579, pp. 1-10, 2014.
[cited by applicant]
Castillo, J. et al., Complex Interaction Between Dengue Virus Replication and Expression of Mirna-133a., BMC Infectious Diseases, vol. 16, 2016.
[cited by applicant]
Champer, J et al., Novel CRISPR/Cas9 Gene Drive Constructs Reveal Insights into Mechanisms of Resistance Allele Formation and Drive Efficiency in Genetically Diverse Populations., PLoS Genetics, 2017.
[cited by applicant]
Chan, Y. et al. Optimising Homing Endonuclease Gene Drive Performance in a Semi-Refractory Species: The
[cited by applicant]
Chan et al., Insect Population Control by Homing Endonuclease-Based Gene Drive: An Evaluation in
[cited by applicant]
Clark et al., Evolution of Genes and Genomes on the
[cited by applicant]
Collins et al., Effects of irradiation dose rate on quality and sterility of Queensland fruit flies,
[cited by applicant]
Condon et al., Genetic sexing through the use of Y-linked transgenes, Insect Biochemistry and Molecular Biology, vol. 37, pp. 1168-1176, 2007.
[cited by applicant]
Curtis et al., Genetic Sex Separation in Anopheles Arabiensis and the Production of Sterile Hybrids, Bulletin in the World of Health Organization, vol. 56, No. 3, pp. 453-454, 1978.
[cited by applicant]
Curtis et al., Genetic Sexing System in
[cited by applicant]
Daborn et al., Evaluating the insecticide resistance potential of eight
[cited by applicant]
Dang et al. Optimizing sgRNA Structure to Improve CRISPR-Cas9 Knockout Efficiency, Genome Biology, vol. 16, No. 280, 2015.
[cited by applicant]
Dicarlo, J. E. et al., Safeguarding CRISPR-Cas9 gene drives in yeast, Nature Biotechnology, vol. 33, No. 12, pp. 1250-1255, 2015.
[cited by applicant]
Doench, J.G. et al., Optimized sgRNA Design to Maximize Activity and Minimize off-Target Effects of CRISPR-Cas9, Nature Biotechnology, vol. 34, No. 2, pp. 184-191, 2016.
[cited by applicant]
Feng, et al. Vanillic acid derivatives from the green algae
[cited by applicant]
Focks et al., An improved separator for the developmental stages, sexes, and species of mosquitoes (
[cited by applicant]
Galizi, R. et al., A synthetic sex ratio distortion system for the control of the human malaria mosquito. Nature Communications, vol. 5, 2012.
[cited by applicant]
Galizi et al., A CRISPR-Cas9 Sex-Ratio Distortion System for Genetic Control, Scientific Reports, vol. 6, No. 31139, 2016.
[cited by applicant]
Gantz et al., Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito
[cited by applicant]
Gantz et al., Highly Efficient Cas9-Mediated Gene Drive for Population Modification of the Malaria Vector Mosquito
[cited by applicant]
Gimble, F. Invasion of a multitude of genetic niches by mobile endonuclease genes, FEMS Microbiology Letters, vol. 185, pp. 99-107, 2000.
[cited by applicant]
Gitzinger et al., The Food Additive Vanillic Acid Controls Transgene Expression in Mammalian Cells and Mice, Nucleic Acids Research, vol. 40, 2012.
[cited by applicant]
Godfray et al., How Driving Endonuclease Genes Can Be Used to Combat Pests and Disease Vectors. BMC Biology, vol. 15, No. 1, pp. 81, 2017.
[cited by applicant]
Gokhale, Chaitanya S., Richard Guy Reeves, and Floyd A. Reed. 2014. “Dynamics of a Combined Medea-Underdominant Population Transformation System.” BMC Evolutionary Biology 14: 98.
[cited by applicant]
Gong et al., “A dominant lethal genetic system for autocidal control of the Mediterranean fruit fly,” Nat. Biotechnol. 23:453-456 (2005).
[cited by applicant]
Gossen et al., “Tight control of gene expression in mammalian cells by tetracycline-responsive promoters,” Proc Natl Acad Sci USA 89:5547-5551 (1992).
[cited by applicant]
Hagmann et al., “The VP16 paradox: Herpes simplex virus VP16 contains a long-range activation domain but within the natural multiprotein complex activates only from promoter-proximal positions,” J Viral 71 :5952-5962 ( …
[cited by applicant]
Hammond, A., R. Galizi, K. Kyrou, A. Simoni, C. Siniscalchi, D. Katsanos, M. Gribble, et al. 2016. “A CRISPR-Cas9 Gene Drive System Targeting Female Reproduction in the Malaria Mosquito Vector Anopheles Gambiae.” Nature…
[cited by applicant]
Handler et al., “Use of the piggyBac transposon for germ-line transformation of insects”, Insect Biochemistry and Molecular Biology, vol. 32, pp. 1211-1220, 2002.
[cited by applicant]
Harwood et al., “The beta-ketoadipate pathway and the biology of self-identity,” Ann Rev Microbial 50:553-590 (1996).
[cited by applicant]
Heravi, et al. “Transcriptional regulation of the van ii late utilization genes (vanABK operon) of Corynebacterium glutamicum by VanR, a PadR-like repressor”, Journal of Bacteriology, JB.02431-14, oo.1-60., (2014).
[cited by applicant]
Hendrichs et al., “Medfly area wide sterile insect technique programmes for preventions, suppression or eradication: The importance of mating behavior studies,” Fla Entomol 85:1-13 (2002).
[cited by applicant]
Hollingdale, M., et al., Nussenzweig, R. S. Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. J. Immunol. 132, pp. 909-913, (1984).
[cited by applicant]
Hongenboom, Melissa, “Genetically modified flies ‘could save crops’”, BBC News, Science and Environment, Aug. 12, 2014. 3 pages.
[cited by applicant]
Huang, Y. et al. Introducing Desirable Transgnes into Insect Populations Using Y-Linked Meiotic Drive? A Tehoretical Assesement, Evolution vol. 61, pp. 717-726.
[cited by applicant]
Issacs, A., et al. Engineered Resistance to Plasmodium falciparum Development in Transgenic Anopheles stephensi. PLOS Pathog. 7, e1002017 (2011 ).
[cited by applicant]
Iwaki et al., “Rapid selection of
[cited by applicant]
Kakkar, et al., “A review on protocatechuic acid and its pharmacological potential.” ISRN pharmacology 2014 (2014).
[cited by applicant]
Kerremans et al., “Use of a Temperature-Sensitive Lethal Mutation Strain of Medfly (
[cited by applicant]
Kim et al., “A genetic sexing strain of
[cited by applicant]
Kim, et al., “Vanillic acid glycoside and quinic acid derivatives from Gardeniae Fructus.” Journal of natural products 69.4 (2006): 600-603.
[cited by applicant]
Koon In, E., et al., Diversity, classification and evolution of CRISPR-Cas systems. Curr. Opin. Microbial. 37, pp. 67-78, (2017).
[cited by applicant]
Koon In, E., et al. Evolutionary Genomics of Defense Systems in Archaea and Bacteria. Annu. Rev. Microbial. 71, 233-261 (2017).
[cited by applicant]
Krafsur et al., “Screwworm eradication is what it seems,” Nature 323:495-496 (1986).
[cited by applicant]
Krafsur et al., “Screwworm eradication in North and Central America,” Parasitology Today 3:131 :137 (1987).
[cited by applicant]
Kuhlman, et al. Combinatorial transcriptional control of the lactose operon of
[cited by applicant]
Labbe et al., “Female-specific flightless (fsRIDL) phenotype for control of Aedes albopictus,” PLoS Neg I Trap Dis 6, e1724 (2012).
[cited by applicant]
Leftwich et al., “Genetic elimination of field-cage populations of Mediterranean fruit flies”, Proc. R. Soc., vol. 281, No. 1792, 21 pages, 2014.
[cited by applicant]
Lewin, Genes V, Oxford University Press, Oxford, pp. 847-873, Fifth Edition.
[cited by applicant]
Li, F. et al. An Anti-Chitinase Malaria Transmission-Blocking Single-Chain Antibody as an Effector Molecule for Creating a Plasmodium falciparum-Refractory Mosquito. J. Infect. Dis. 192, pp. 878-887 (2005).
[cited by applicant]
Lines et al., “Genetic sexing systems in Anopheles arabiensis Patton (Diptera: Culicidae)”, Journal of Economic Entomology, vol. 78, pp. 848-851, 1985.
[cited by applicant]
Lyttle, T. Experimental population genetics of meiotic drive systems I. Pseudo-Y chromosomal drive as a means of eliminating cage populations of
[cited by applicant]
Magnusson et al., “Transcription regulation of sex-biased genes during ontogeny in the malaria vector Anopheles gambiae”, PLoS One, vol. 6, No. 6, e21572, 2011.
[cited by applicant]
Malavasi, A. Project Aedes transgenic population control in Juazeiro and, Jacobina Bahia, Brazil. BMC Proc. 8, 011 (2014).
[cited by applicant]
Marois et al. High-throughput sorting of mosquito larvae for laboratory studies and for future vector control interventions, Malaria Journal, vol. 11, No. 1, pp. 302-308, 2012.
[cited by applicant]
Marshall, J. et al.The Impact of Dissociation on Transposon-Mediated Disease Control Strategies. Genetics vol. 178, pp. 1673-1682 (2008).
[cited by applicant]
Martinez et al., Biodegradation of lignocellulosics: microbial, chemical, and enzymatic aspects of the fungal attack of lignin, Int Microbiol 8:195-204 (2005).
[cited by applicant]
Mathur, G. et al., Transgene-mediated suppression of dengue viruses in the salivary glands of the yellow fever mosquito,
[cited by applicant]
McCauley, et al., Analysis of a Human Sperm CD52 Glycoform in Primates: Identification 1-30 of an Animal Model for Immunocontraceptive Vaccine. Development, Biology of Reproduction, vol. 66, DD. 1681-1688, (2002).
[cited by applicant]
McDonald et al., “A Genetic-Sexing Strain Based on Malathion Resistance for Culex-Tarsalis”, Mosquito News, vol. 42, No. 4, pp. 531-536, 1982.
[cited by applicant]
Medici et al., “Studies on Aedes albopictus larval mass-rearing optimization”, Journal of Economic Entomology, vol. 104, No. 1, pp. 266-273, 2011.
[cited by applicant]
Merkens et al., Vanillate metabolism in Corynebacterium glutamicum, Curr Microbial 51 :59-65 (2005).
[cited by applicant]
Morrison et al., “Engineered repressible lethality for controlling the pink bollworm, a lepidopteran pest of cotton,” PLoS One 7:e50922 (2012).
[cited by applicant]
Nishimura et al., “Molecular cloning of Streptomyces genes encoding vanillate demethylase,” Biosci Biotech Bioch 70:2316-2319 (2006).
[cited by applicant]
Noble, C. et al., “Evolutionary dynamics of CRISPR gene drives”, Science Advances, 5, vol. 3, e1601964, (2017.
[cited by applicant]
Nuckolls, N. L., M. A. Bravo Nunez, M. T. Eickbush, J. M. Young, J. J. Lange, J. S. Yu, G. R. Smith, S. L. Jaspersen, H. S. Malik, and S. E. Zanders. 2017. “Wtf Genes Are Prolific Dual Poison-Antidote Meiotic Drivers.” …
[cited by applicant]
Oberhofer, G. et al., Behavoir for Homin Endoclease Gene Drives targeting Genes Required for Viability or Femal Fertility with Multiplexted Guide RNAs, (2018).
[cited by applicant]
Papathanos et al., “Sex Ratio Manipulation for Insect Population Control”, Transgenic Insects: Techniques and Applications, pp. 83-100, Publication date Oct. 29, 2014.
[cited by applicant]
Papathanos, et al., “Sex Separation Strategies: past experience and new approaches”, Malaria Journal, vol. 8, Suppl 2, No. S5, 2009.
[cited by applicant]
Pomiankowski et al., “The evolution of the
[cited by applicant]
Poindexter, “Biological properties and classification of the Caulobacter group,” Bacterial Rev 28:231-295 (1964).
[cited by applicant]
Popovic!, J. et al., Assessing key safety concerns of a Wolbachia-based strategy to control dengue transmission by Aedes mosquitoes. Mem. Inst. Oswaldo Cruz 105, pp. 957-964, (2010).
[cited by applicant]
Port, F. et al., Optimized CRISPR/Cas Tools for Efficient Germline and Somatic Genome Engineering in
[cited by applicant]
Preston, Christine R., Carlos C. Flores, and William R. Engels. 2006. “Differential Usage of Alternative Pathways of Double-Strand Break Repair in
[cited by applicant]
Rendon et al., “Medfly (
[cited by applicant]
Resnik, D., Ethical Issues in Field Trials of Genetically Modified Disease-Resistant Mosquitoes, Dev. World Bioeth, vol. 14, pp. 37-46, (2014).
[cited by applicant]
Robinson et al., “Cytological, linkage and insecticide studies on a genetic sexing line in Anopheles stephensi Liston”, Heredity, vol. 58, pp. 95-101, 1987.
[cited by applicant]
Royden, C., et al., The Tko Locus, Site of a Behavioral Mutation in
[cited by applicant]
Sambrook et al., Molecular Cloning, a Laboratory Manual, Cold Springs Harbor Press, Cold Springs Harbor, N. Y. 1989, Second Edition.
[cited by applicant]
Seawright et al., “Genetic method for the preferential elimination of females of anopheles albimanus”, Science, vol. 200, No. 4347, pp. 1303-1304, 1978.
[cited by applicant]
Sebrovskii, A. et al. A New Possible Method of Pest Control. Zool Zh, vol. 19, pp. 618-630, (1940).
[cited by applicant]
Segura et al., “Genetic analysis of a chromosomal region containing vanA and vanB, genes required for conversion of either ferulate or vanillate to protocatechuate in Acinetobacter,” J Bacterial 181 :3494-3504 (1999).
[cited by applicant]
Seidel, H. S., M. Ailion, J. Li, A. van Oudenaarden, M. V. Rockman, and L. Kruglyak. 2011. “A Novel Sperm-Delivered Toxin Causes Late-Stage Embryo Lethality and Transmission Ratio Distortion in C. Elegans.” PLoS Biology…
[cited by applicant]
Shaner, N. et al., Improved Monomeric Red, Orange and Yellow Fluorescent Proteins Derived from
[cited by applicant]
Sh etty, “Genetic sexing system for the preferential elimination of females in Cu lex quinquefasciatus”, Journal of the American Mosquito Control Association, vol. 3, No. 1, pp. 84-86, 1987.
[cited by applicant]
Shmakov, S. et al., Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems. Mol. Cell 60, 385-397 (2015).
[cited by applicant]
Shmakov, S. et al., Diversity and evolution of class 2 CRISPR-Cas systems. Nat. Rev. Microbial. 15, pp. 169-182 (2017).
[cited by applicant]
Simoni, A. et al., Development of synthetic selfish elements based on modular nucleases in
[cited by applicant]
Singleton et al., Title Page of Dictionary of Microbiology and Molecular Biology, J. Wiley & Sons, New York, N. Y., 1994, Second Edition.
[cited by applicant]
Steller et al., “A Transposable P Vector That Confers Selectable G418 Resistance to
[cited by applicant]
Sun, N., and H. Zhao. 2014. “A Single-Chain TALEN Architecture for Genome Engineering.” Molecular bioSystems 10 (3): 446-53.
[cited by applicant]
Thanbichler et al., “A comprehensive set of plasmids for van ii late- and xylose-inducible gene expression in Caulobacter crescentus,” Nucleic Acids Res 35:e137 (2007).
[cited by applicant]
Travanty, E., et al., Using RNA interference to develop dengue virus resistance in genetically modified Aedes aegypti. Insect Biochem. Mol. Biol. 34, pp., 607-613, (2004).
[cited by applicant]
Wade, M. J., and R. W. Beeman. 1994. “The Population Dynamics of Maternal-Effect Selfish Genes.” Genetics 138 (4): 1309-14.
[cited by applicant]
Ward, Catherine M., Jessica T. Su, Yunxin Huang, Alun L. Lloyd, Fred Gould, and Bruce A. Hay. 2011. “Medea Selfish Genetic Elements as Tools for Altering Traits of Wild Populations: A Theoretical Analysis.” Evolution; I…
[cited by applicant]
WHO World Malaria Report dated 2014, accessed on the world wide web at <Who. int/malaria/publications/world_ malaria_report_ 2014/en/>.
[cited by applicant]
Yamada et al., “Genetic sex separation of the malaria vector, Anopheles arabiensis, by exposing eggs to dieldrin”, Malaria Journal, vol. 11, No. 1, pp. 208-219, 2012.
[cited by applicant]
Yen, P. et al. Synthetic miRNAs induce dual arboviral-resistance phenotypes in the vector mosquito
[cited by applicant]
Zeh et al., “From father to son: transgenerational effect of tetracycline on sperm viability,” Sci Rep 2:375 (2012).
[cited by applicant]
File History of U.S. Appl. No. 14/170,118.
[cited by applicant]
File History of U.S. Appl. No. 14/206,011.
[cited by applicant]
File History of U.S. Appl. No. 14/631,171.
[cited by applicant]
File History of U.S. Appl. No. 14/837,941.
[cited by applicant]
File History of U.S. Appl. No. 15/970,728.
[cited by applicant]
Akbari, O.S. et al., A synthetic gene drive system for local, reversible modification and suppression of insect populations, Curr. Biol., vol. 23 No. 8, pp. 671-677. 2013.
[cited by applicant]
Akbari, O.S. et al., Novel synthetic Medea selfish genetic elements drive population replacement in
[cited by applicant]
Alphey, L. et al., Malaria Control with Genetically Manipulated Insect, Nature vol. 415, 702; 2002.
[cited by applicant]
Al Trock, P. M. et al., Stability properties of underdominance in finite subdivided populations, PLoS Comput. Biol., vol. 7 No. 11, e1002260; 2011.
[cited by applicant]
Altrock, P. M. et al., Using underdominance to bi-stably transform local populations, J Theor Biol, vol. 267 No. 1, pp. 62-75; 2010.
[cited by applicant]
Arndt, K. M. et al., Helix-stabilized Fv (hsFv) antibody fragments: substituting the constant domains of a Fab fragment for a heterodimeric coiled-coil domain, J Mol Biol, vol. 312 No. 1, pp. 221-228.; 2001.
[cited by applicant]
Asman, S. M. et al., Field studies of genetic control systems for mosquitoes, Annu Rev Entomol., vol. 26 No. 1, pp. 289-318; 1981.
[cited by applicant]
Baker, R.H., Chromosome Rearrangements in the Control of Mosquitos, Prev Vet Med 2, pp. 529-540; 1984.
[cited by applicant]
Bergmann, A. et al., The
[cited by applicant]
Beumer, K. J. et al., “Induced chromosomal exchange directs the segregation of recombinant chromatids in mitosis of
[cited by applicant]
Bier V.M.G.A.E et al., The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations, Science, vol. 348 No. 6233, pp. 442-444; 2015.
[cited by applicant]
Billeter, J. C. et al., Specialized cells tag sexual and species identity in
[cited by applicant]
Boete C. et al., A theoretical approach to predicting the success of genetic manipulation of malaria mosquitoes in malaria control, Malar J, vol. 1 No. 3; 2002.
[cited by applicant]
Boete C. et al., Evolutionary ideas about genetically manipulated mosquitoes and malaria control, Trends Parasitol, vol. 19 No. 1, pp. 32-38; 2003.
[cited by applicant]
Bohannon J., Food aid. Zambia rejects GM corn on scientists' advice, Science, vol. 298 No. 5596, pp. 1153-1154;2002.
[cited by applicant]
Borycz J. et al., ABC transporter mutants white, brown and scarlet have altered contents and distribution of biogenic amines in the brain, J Exp Biol, vol. 211 No. 21, pp. 3454-3466; 2008.
[cited by applicant]
Braig, H. R. et al., The spread of genetic constructs in natural insect populations. In D. K. Letourneau & B. E. Burrows (Eds.) Genetically Engineered Organisms: Assessing Environmental and Human Health Effects (pp. 251…
[cited by applicant]
Carvajal-Vallejos P. et al., Unprecedented rates and efficiencies revealed for new natural split inteins from metagenomic sources, J Biol Chem, vol. 287 No. 34, pp. 28686-28696; 2012.
[cited by applicant]
Carvalho D.O. et al., Two step male release strategy using transgenic mosquito lines to control transmission of vector-borne diseases, Acta Trop 132S, S170-S177; 2014.
[cited by applicant]
Chen C.H. et al., A synthetic maternal-effect selfish genetic element drives population replacement in
[cited by applicant]
Cheriyan, M. et al., Faster protein splicing with the Nostoc punctiforme DnaE intein using non-native extein residues, J Biol Chem, vol. 288 No. 9, pp. 6202-6211; 2013.
[cited by applicant]
Cook, R. K. et al., The generation of chromosomal deletions to provide extensive coverage and subdivision of the
[cited by applicant]
Corby-Harris, V. et al., Activation of Akt signaling reduces the prevalence and intensity of malaria parasite infection and lifespan in
[cited by applicant]
Crompton, P. D. et al., Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease, Annu Rev of Immunol, vol. 32 No. 1, pp. 157-187; 2014.
[cited by applicant]
Curtis C.F. et al., “Computer simulation of the use of double translocations for pest control,” Genetics, vol. 69 No. 1, 97-113; 1971.
[cited by applicant]
Curtis, C. F., Possible use of translocations to fix desirable genes in insect pest populations, Nature, vol. 218 No. 5139, pp. 368-369; 1968.
[cited by applicant]
Dantuma N.P. et al., Short-lived green fluorescent proteins for quantifying ubiquitin/proteasomedependent proteolysis in living cells, Nat Biotechnol., vol. 18 No. 5, pp. 538-543; 2000.
[cited by applicant]
Davis S. et al., Engineered underdominance allows efficient and economical introgression of traits into pest populations, J Theor Biol., vol. 212 No. 1, pp. 83-98; 2010.
[cited by applicant]
De Jesus C. et al., Use of genetic modified mosquitoes to fight dengue in Brazil, International Journal of Research in Pharmaceutical and Nano Sciences, vol. 2 No. 6, pp. 811-816; 2000.
[cited by applicant]
De La Rocque S. et al., A review of trends in the distribution of vector-borne diseases: is international trade contributing to their spread? Rev Sci Tech, vol. 30 No. 1, pp. 119-130; 2011.
[cited by applicant]
De Lara Capurro M. et al., Virus-expressed, recombinant single-chain antibody blocks sporozoite infection of salivary glands in Plasmodium gallinaceum-infected Aedes aegypti, Am J Trop Med Hyg., vol. 62 No. 4, oo. 427-4…
[cited by applicant]
Den. et al., Highly complementary target RNAs promote release of guide RNAs from human Argonaute2, Mol Cell, vol. 50 No. 3, pp. 344-355; 2013.
[cited by applicant]
Deredec A et al., The population genetics of using homing endonuclease genes in vector and pest management, Genetics, vol. 179 No. 4, pp. 2013-2026; 2008.
[cited by applicant]
Dhar T. et al., Modification of transmembrane and GP I-anchored proteins on living cells by efficient protein trans-splicing using the Npu DnaE intein, Chem Commun (Camb), vol. 47 No. 11, pp. 3063-3065; 2011.
[cited by applicant]
Egli D et al., An efficient method to generate chromosomal rearrangements by targeted DNA doublestrand breaks in
[cited by applicant]
Enayati A. et al., Malaria management: past, present, and future, Annu Rev Entomol., vol. 55, pp. 569-591; 2010.
[cited by applicant]
Engler, C. et al., A one pot, one step, precision cloning method with high throughput capability, PLoS one, vol. 3 No. 11, e3647; 2008.
[cited by applicant]
Engler, C. et al., Golden gate shuffling: a one-pot DNA shuffling method based on type IIs restriction enzymes, PLoS one, vol. 4 No. 5, e5553; 2009.
[cited by applicant]
Eppstein, M. J., Payne, J. L., & Goodnight, C. J. (2009). Underdominance, multiscale interactions, and self-organizing barriers to gene flow. Journal of Artificial Evolution and Applications 5, 1-13.
[cited by applicant]
Esvel T, K.M. et al., Concerning RNA-guided gene drives for the alteration of wild populations, Elife, e03401; 2014.
[cited by applicant]
Fields, S. et al., A novel genetic system to detect protein-protein interactions, Nature, vol. 340 No. 6230, pp. 245-246; 1989.
[cited by applicant]
Filipowicz, W. et al., Post-transcriptional gene silencing by siRNAs and miRNAs, Curr Opin Struct Biol., vol. 15 No. 3, pp. 331-341; 2005.
[cited by applicant]
Forster, A. et al., Chromosomal translocation engineering to recapitulate primary events of human cancer, Cold Spring Harb Symp Quant Biol, vol. 70, pp. 275-282; 2005.
[cited by applicant]
Foster, G. et al., Chromosome rearrangements for the control of insect pests, Science, vol. 176 No. 4037, pp. 875-880; 1972.
[cited by applicant]
Franz, A. W. et al., Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti, Proc Natl Acad Sci US A, vol. 103 No. 11, pp. 4198-4203; 2006.
[cited by applicant]
Fu, G. et al., Female-specific flightless phenotype for mosquito control, Proc Natl Acad Sci USA, vol. 107 No. 10, pp. 4550 -˜554; 2010.
[cited by applicant]
Gallup, J.L. et al., The economic burden of malaria, Am J Trop Med Hyg, vol. 64 No. 1-2 Suppl, pp. 85-96; 2001.
[cited by applicant]
Gdula, D.A. et al., Genetic and molecular analysis of the gypsy chromatin insulator of
[cited by applicant]
Gibson, D. G. et al., Enzymatic assembly of DNA molecules up to several hundred kilobases, Nat Methods, vol. 6 No. 5, pp. 343-345; 2009.
[cited by applicant]
Githeko, A. K. et al., Climate change and vector-borne diseases: a regional analysis, Bulletin of the World Health Organization, vol. 78, No. 9, pp. 1136-1147, 2000.
[cited by applicant]
Gong, W. J. et al., Ends-out, or replacement, gene targeting in
[cited by applicant]
Gould, F. et al., Population genetics of autocidal control and strain replacement, Annu Rev Entomol, vol. 49, pp. 193-217, 2004.
[cited by applicant]
Gould, F. et al., A Killer-Rescue system for selflimiting gene drive of anti-pathogen constructs, Proceedings of the Royal Society B: Biological Sciences, vol. 275, No. 1653, pp. 2823-2829, 2008.
[cited by applicant]
Gould, F. et al., Genetic strategies for controlling mosquitoborne diseases: engineered genes that block the transmission of malaria and dengue can hitch a ride on selfish DNA and spread into wild populations, American …
[cited by applicant]
Groth, A. C. et al., Construction of transgenic
[cited by applicant]
Gubler, D. J. et al., Climate variability and change in the United States: potential impacts on vector and rodent-borne diseases, Environmental health perspectives, vol. 109, Suppl 2, pp. 223, 2001.
[cited by applicant]
Gubler, D. J., Resurgent vector-borne diseases as a global health problem, Emerging infectious diseases, vol. 4, No. 3, pp. 442, 1998.
[cited by applicant]
Gutierrez, E. et al., Specialized hepatocytelike cells regulate
[cited by applicant]
Han, Z. et al., Hand is a direct target ofTinman and GATA factors during
[cited by applicant]
Harris, A. F. et al., Field performance of engineered male mosquitoes, Nature biotechnology, vol. 29, No. 11, pp. 1034-1037, 2011.
[cited by applicant]
Harris, A. F. et al., Successful suppression of a field mosquito population by sustained release of engineered male mosquitoes, Nature biotechnology, vol. 30, No. 9, pp. 828-830, 2012.
[cited by applicant]
Hartl, D.L. et al., Principles of Population Genetics, Sunderland, MA: Sinauer Associates, Inc., 1997.
[cited by applicant]
Hay, B. A. et al., Engineering the genomes of wild insect populations: challenges, and opportunities provided by synthetic Medea selfish genetic elements, J Insect Physiol, vol. 56, No. 10, pp. 1402-1413, 2010.
[cited by applicant]
Hoffmann, A. A. et al., Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission, Nature, vol. 476, No. 7361, pp. 454-457, 2011.
[cited by applicant]
Ito, J. et al. Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite, Nature, vol. 417, No. 6887, pp. 452-455, 2002.
[cited by applicant]
Jacobs-Lorena, M. Genetic approached for malaria control. In Bogers, R.J. (ed.), Bridging Laboratory and Field Research for Genetic Control of Disease Vectors, pp. 52-65, Retrieved from htto://librarv.wur.nl/frontis/, 2…
[cited by applicant]
James, A. A, Gene drive systems in mosquitoes: rules of the road, Trends Parasitol, vol. 21, No. 2, pp. 64-67, 2005.
[cited by applicant]
Jansen V.A. et al., Stochastic spread of Wolbachia, Proc Biol Sci, vol. 275 No. 1652, pp. 2769-2776; 2008.
[cited by applicant]
Kaiser, P.E. et al., Radiation induced reciprocal translocations and inversions in Anopheles albimanus, Can J Genet Cytol, vol. 24 No. 2, pp. 177-188; 1982.
[cited by applicant]
Kim, W. et al., Ectopic expression of a cecropin transgene in the human malaria vector mosquito
[cited by applicant]
Knols, B. G. et al., Transgenic mosquitoes and the fight against malaria: managing technology push in a turbulent GMO world, Am J Trop Med Hyg., vol. 77, 6 Suppl, pp. 232-242, 2007.
[cited by applicant]
Krafsur, E. S. et al., Sterile insect technique for suppressing and eradicating insect populations: 55 years and counting, J, Agr. Entomol., vol. 15, 303-317, 1998.
[cited by applicant]
Krstic, D. et al., Influence of the White Locus on the Courtship Behavior of
[cited by applicant]
Kwit, C. et al., Transgene introgression in crop relatives: molecular evidence and mitigation strategies. Trends Biotechnol, vol. 29, No. 6, pp. 284-293, 2011.
[cited by applicant]
Kyrchanova, 0., et al., Orientation-dependent interaction between
[cited by applicant]
Lambrechts, L. et al., Can transgenic mosquitoes afford the fitness cost? Trends Parasitol, vol. 24 No. 1, pp. 4-7; 2008.
[cited by applicant]
Lemon, S. M. et al., Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections, Workshop Summary (Forum on Microbial Threats), National Academies Press, 2008.
[cited by applicant]
Lin, H. et al., Cellular toxicity induced by SRFmediated transcriptional squelching, Toxicological sciences, vol. 96, No., 1, pp. 83-91, 2007.
[cited by applicant]
Lo, P. C. et al., A role for the COUP-TF-related gene seven-up in the diversification of cardioblast identities in the dorsal vessel of
[cited by applicant]
Lockless, S, W, et al., Traceless protein splicing utilizing evolved split inteins, Proc Natl Acad Sci U SA, vol. 106, No. 27, pp. 10999-11004, 2009.
[cited by applicant]
Luan, H. et al., Refined spatial manipulation of neuronal function by combinatorial restriction of transgene expression, Neuron, vol. 52, No. 3, pp. 425-436, 2006.
[cited by applicant]
Lyon, M. F, et al., Mutagenlc effects of repeated small radiation doses to mouse spermatogonla I. Specific-locus mutation rates, Mutation Research/Fun'damental and Molecular Mechanisms of Mutagenesis, vol. 15, No. 2, DD…
[cited by applicant]
Magori, K. et al., Genetically engineered underdominance for manipulation of pest populations: a deterministic model. Genetics, vol. 172, No. 4, pp. 2613-2620, 2006.
[cited by applicant]
Marris, E., Transgenic fish go large, Nature, vol. 467, No. 7313, pp. 259, 2010.
[cited by applicant]
Marshall, J. M. et al., Confinement of gene drive systems to local populations: a comparative analysis, J Theor Biol, vol. 294, pp. 153-171, 2012.
[cited by applicant]
Marshall, J. M. et al., Inverse Medea as a novel gene drive system for local population replacement: a theoretical analysis, J Hered, vol. 102, No. 3, pp. 336-341, 2011.
[cited by applicant]
Marshall, J. M. et al., Perspectives of people in Mali toward genetically-modified mosquitoes for malaria control, Malar J, vol. 9, No. 128, 201 0a.
[cited by applicant]
Marshall, J. M. et al., Towards a quantitative assessment of public attitudes to transgenic mosquitoes: Questions based on a qualitative survey in Mali, Asia Pacific J. Mol. Biol. Biotechnol, vol. 18, pp. 251-273, 2010b.
[cited by applicant]
Marshall, J. M., The Cartagena Protocol and genetically modified mosquitoes, Nat. Biotechnol., vol. 28, No. 9, pp. 896-897, 2010.
[cited by applicant]
Marshall, J. M., The effect of gene drive on containment of transgenic mosquitoes, J. of Theor. Biol., vol. 258, No. 2, pp. 250-265, 2009.
[cited by applicant]
Marshall, J.M. et al., General principles of single-construct chromosomal gene drive, Evolution; vol. 66 No. 7, pp. 2150-2166; 2012b.
[cited by applicant]
Marshall, J.M. et al., Samele: a killer-male, rescue-female system for suppression and replacement of insect disease vector populations, Genetics, vol. 187 No. 2, pp. 535-551; 2011.
[cited by applicant]
Marygold, S. J. et al., The ribosomal protein genes and Minute loci of
[cited by applicant]
Matzen, K.J. Engineering of Dengue virus refractoriness in Aedes aegypti and development of an underdominant gene drive system (Doctoral dissertation), California Institute of Technology, Pasadena, CA, 2012.
[cited by applicant]
McManus, M. T. et al., Gene silencing using micro-RNA designed hairpins, RNA, vol. 8, No. 6, 842-850, 2002.
[cited by applicant]
Miller, L. H. et al., Perspective on malaria eradication: is eradication possible without modifying the mosquito? Journal of Infectious Diseases, vol. 200, No., 11, pp. 1644-1645, 2009.
[cited by applicant]
Miller, T. A., Let high-tech genetically modified insects counter dengue, BioScience, vol. 61, No. 8, pp. 586-587, 2011.
[cited by applicant]
Moreira, L.A. et al., Bee venom phospholipase inhibits malaria parasite development in transgenic mosquitoes, J Biol Chem, vol. 277, No. 43, pp. 40839-40843, 2002.
[cited by applicant]
Moreno, E., Design and construction of “synthetic species,” PLoS One, vol. 7, No. 7, e39054, 2012.
[cited by applicant]
Morrison, N. I. et al., Genetic improvements to the sterile insect technique for agricultural pests, Asia-Pacific Journal of Molecular Biology and Biotechnology, vol. 18, No. 2, pp. 275-295, 2010.
[cited by applicant]
Mumford, J. D. Science, regulation, and precedent for genetically modified insects, PLoS neglected tropical diseases, vol. 6, No. 1, e1504, 2012.
[cited by applicant]
Murray, C. J. et al., Global malaria mortality between 1980 and 201 O: a systematic analysis, The Lancet, vol. 379, No. 9814, pp. 413-431, 2012.
[cited by applicant]
Nath, R., Generation and characterisation of plant produced recombinant antibodies specific to LHRH for treatment of sex hormone dependent diseases. (MS thesis), Fachhochschule Aachen, Aachen, Germany, 2003.
[cited by applicant]
Ndiath, M. 0., et al., Resistance to DDT and pyrethroids and increased kdr mutation frequency in an. gambiae after the implementation of permethrin-treated nets in Senegal, PloS one, vol. 7, No. 2, e31943, 2012.
[cited by applicant]
Neely, G. G. et al., A Global In Vivo Drosophila RNAi Screen Identifies NOT3 as a Conserved Regulator of Heart Function, Cell, vol. 141, No. 1, pp. 142-153, 2010.
[cited by applicant]
Nern, A. et al., Multiple new site-specific recombinases for use in manipulating animal genomes, Proceedings of the National Academy of Sciences, vol. 108, No. 34, pp. 14198-14203, 2011.
[cited by applicant]
Ni, J. Q. et al., A genome-scale shRNA resource for transgenic RNAi in
[cited by applicant]
Nicholson, G.M. et al., Fighting the global pest problem: preface to the special Toxicon issue on insecticidal toxins and their potential for insect pest control, Toxicon, vol. 49 No, 4, pp. 413-422; 2007.
[cited by applicant]
Oye, K.A et al., Biotechnology. Regulating gene drives, Science vol. 345 No. 6197, pp. 626-628; 2014.
[cited by applicant]
Pardo, R. et al., The role of means and goals in technology acceptance, a differentiated landscape of public perceptions of pharming, EMBO Rep, vol. 10, No. 10, pp. 1069-1075, 2009.
[cited by applicant]
Parvy, J. P. et al.,
[cited by applicant]
Perri Mon, N. et al., In vivo RNAi: today and tomorrow, Cold Spring Harbor perspectives in biology, vol. 2, No. 8, a003640, 2010.
[cited by applicant]
Pfeiffer, B. D. et al., Refinement of tools for targeted gene expression in
[cited by applicant]
Pfeiffer, B. D. et al., Using translational enhancers to increase transgene expression in
[cited by applicant]
Ran, F. A. et al., Genome engineering using the CRISPR-Cas9 system, Nature protocols, vol. 8, No. 11, pp. 2281-2308, 2013.
[cited by applicant]
Randolph, S.E. et al., “The arrival, establishment and spread of exotic diseases: patterns and predictions,” Nat Rev Microbiol., vol. 8 No. 5, pp. 361-371; (2010).
[cited by applicant]
Riehle, M. M. et al., Anopheles gambiae APL 1 is a family of variable LRR proteins required for Rel1-mediated protection from the malaria parasite, Plasmodium berghei, PLoS One, vol. 3, No. 11, e3672, 2008.
[cited by applicant]
Ringrose, L., et al., Quantitative comparison of DNA looping in vitro and in vivo: chromatin increases effective DNA flexibility at short distances, The EMBO Journal, vol. 18, No. 23, 6630-6641, 1999.
[cited by applicant]
Robinson A.S., A reassessment of the use of chromosome inversions for insect control, Journal of Heredity, vol. 66, pp. 35-37, 1975.
[cited by applicant]
Robinson, A. S. et al., Insect transgenesis and its potential role in agriculture and human health, Insect biochemistry and molecular biology, vol. 34, No. 2, pp. 113-120, 2004.
[cited by applicant]
Robinson, A.S. et al., Controlled Crosses and Cage Experiments with a Translocation in
[cited by applicant]
Robinson, A.S., Progress in the use of chromosomal translocations for the control of insect pests. Biological Reviews, vol. 51, No. 1, pp. 1-24, 1976.
[cited by applicant]
Rong, Y. S. et al., The homologous chromosome is an effective template for the repair of mitotic DNA double-strand breaks in
[cited by applicant]
Rorth, P, Gal4 in the
[cited by applicant]
Schmid-Hempel, P., Evolutionary ecology of insect Immune defenses, Annu Rev Entomol, vol. 50, pp. 529-551, 2005.
[cited by applicant]
Schnutgen, F. et al., Adopting the good reFLEXes when generating conditional alterations in the mouse genome, Transgenic research, vol. 16, No. 4, pp. 405-413, 2007.
[cited by applicant]
Schwartz, E. C. et al., Post-translational enzyme activation in an animal via optimized conditional protein splicing, Nat Chem Biol, vol. 3, No. 1., pp. 50-54, 2007.
[cited by applicant]
Sellin, J. et al., Dynamics of heart differentiation, visualized utilizing heart enhancer elements of the
[cited by applicant]
Sherizen, D. et al., Meiotic recombination in
[cited by applicant]
Sinkins, S. P. et al., Gene drive systems for insect disease vectors, Nat Rev Genet, vol. 7, No. 6, pp. 427-435, 2006.
[cited by applicant]
Spradling, A. C. et al., Transposition of cloned P elements into
[cited by applicant]
Szymczak, A. L. et al., Correction of multi-gene deficiency in vivo using a single‘self-cleaving’ 2A peptide-based retroviral vector, Nature biotechnology, vol. 22, No. 5, pp. 589-594, 2004.
[cited by applicant]
Tatem, A.J. et al., Global transport networks and infectious disease spread, Adv Parasitol, vol. 62, pp. 293-343; 2006.
[cited by applicant]
Theilmann, D.A. et al., Molecular analysis of the trans-activating IE-2 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosls virus, Virology, vol. 187, No. 1, pp. 84-96, 1992.
[cited by applicant]
Thomas, D. D. et al., Insect population control using a dominant, repressible, lethal genetic system. Science, vol. 287, No. 5462, pp. 2474-2476, 2000.
[cited by applicant]
Thorpe, H. M. et al., Control of directionality in the sitespecific recombination system of the Streptomyces phage cpC31, Molecular microbiology, vol. 38, No. 2, pp. 232-241, 2000.
[cited by applicant]
Tolle, M. A., Mosquito-borne diseases. Current problems in pediatric and adolescent health care, vol. 39, No. 4, pp. 97-140, 2009.
[cited by applicant]
Tripet, F. et al., Ecological immunology of mosquito-malaria interactions, Trends Parasitol vol. 24 No. 5-3, pp. 219-227; 2008.
[cited by applicant]
Uemura, M. et al., Chromosomal manipulation by site-specific recombinases and fluorescent protein based vectors, PioS one vol. 5 No. 3, e9846; 2010.
[cited by applicant]
Van Dyke, D. L. et al., The frequency and mutation rate of balanced autosomal rearrangements In man estimated from prenatal genetic studies for advanced maternal age, American journal of human Qenetics, vol. 35, No. 2, …
[cited by applicant]
Walker, T. et al., The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations, Nature, vol. 476, No. 7361, pp. 450-453, 2011.
[cited by applicant]
Wang, S. et al., Genetic approaches to interfere with malaria transmission by vector mosquitoes, Trends in biotechnology, vol. 31, No. 3, pp. 185-193, 2013.
[cited by applicant]
Weber, E. et al., A modular cloning system for standardized assembly of multigene constructs, PLoS one, vol. 6, No. 2, e16765, 2011.
[cited by applicant]
Whitten, M. J., Insect control by genetic manipulation of natural populations, Science, vol. 171, No. 3972, pp. 682-684, 1971.
[cited by applicant]
Willis, N.L. et al., Reciprocal translocations and partial correlation of chromosomes in the stable fly, J Hered vol. 72 No. 2, pp. 104-106; 1981.
[cited by applicant]
Windbichler, N. et al., A synthetic homing endonuclease-based gene drive system in the human malaria mosquito, Nature, vol. 473, No. 7346, pp. 212-215, 2011.
[cited by applicant]
World Health Organization Global Burden of Disease Study, Retrieved Apr. 30, 2014, from who.int/evidence/bod, 2000.
[cited by applicant]
Yu, Y. et al., Engineering chromosomal rearrangements in mice, Nat Rev Genet, vol. 2, No. 10, pp. 780-790, 2001.
[cited by applicant]
Zettler, J. et al., The naturally split Npu DnaE intein exhibits an extraordinarily high rate in the protein trans-splicing reaction, FEBS Lett, vol. 583, No. 5, pp. 909-914, 2009.
[cited by applicant]
Zhou, X. et al., Optimization of the Tet-On system for regulated gene expression through viral evolution, Gene therapy, vol. 13, No. 19, pp. 1382-1390, 2006.
[cited by applicant]
Zhu, X. D. et al., Cleavage-dependent ligation by the FLP recombinase; characterization of a mutant flp protein with an alteration in a catalytic amino acid, Journal of Biological Chemistry, vol. 270, No. 39, pp. 23044-…
[cited by applicant]
Restriction Requirement Dated Feb. 23, 2015 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Office Action Dated Apr. 9, 2015 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Restriction Requirement Dated Sep. 14, 2015 in U.S. Appl. No. 14/631,171.
[cited by applicant]
Office Action Dated Sep. 21, 2015 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Advisory Action Dated Dec. 31, 2015 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Office Action Dated Feb. 4, 2016 in U.S. Appl. No. 14/631,171.
[cited by applicant]
Office Action Dated Apr. 7, 2016 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Office Action Dated Jun. 2, 2016 in U.S. Appl. No. 14/170,118.
[cited by applicant]
Office Action Dated Aug. 18, 2016 in U.S. Appl. No. 14/631,171.
[cited by applicant]
Office Action Dated Sep. 2, 2016 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Advisory Action Dated Nov. 21, 2016 in U.S. Appl. No. 14/206,011.
[cited by applicant]
Office Action Dated Dec. 28, 2016 in U.S. Appl. No. 14/170,118.
[cited by applicant]
Office Action Dated Apr. 6, 2017 in U.S. Appl. No. 14/631,171.
[cited by applicant]
Office Action Dated Sep. 21, 2017 in U.S. Appl. No. 14/837,941.
[cited by applicant]
Office Action Dated Jan. 26, 2018 in U.S. Appl. No. 14/837,941.
[cited by applicant]
Office Action Dated Aug. 24, 2018 U.S. Appl. No. 14/837,941.
[cited by applicant]
Office Action Dated Oct. 19, 2018 in U.S. Appl. No. 14/170,118.
[cited by applicant]
International Search Report and Written Opinion Mailed Apr. 25, 2014 in International Application No. PCT/US2014/013943.
[cited by applicant]
Notice of Allowance dated May 29, 2020 in U.S. Appl. No. 15/164,452.
[cited by applicant]
File History of U.S. Appl. No. 15/164,452.
[cited by applicant]
A Phase 1, Randomized, Blinded, Dose-escalation Study of rAAV1-PG9DP Recombinant AAV Vector Coding for PG9 Antibody in Healthy Male Adults (ClinicalTrials.gov Identifier: NCT01937455.
[cited by applicant]
Advisory Action Dated Mar. 1, 2019 in U.S. Appl. No. 14/170,118.
[cited by applicant]
Advisory Action Dated Mar. 7, 2017 in U.S. Appl. No. 14/170,118.
[cited by applicant]
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