Granted Patent
B2
US 12,251,429 · App. 17/017,037 · Granted Mar 18, 2025
Methods and compositions for RNA-guided treatment of HIV infection
Inventors:
Kamel Khalili (Bala Cynwyd, PA); Wenhui Hu (Cherry Hill, NJ); Yonggang Zhang (Maple Shade, NJ)
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Compositions for specifically cleaving target sequences in retroviruses include nucleic acids encoding a Clustered Regularly Interspace Short Palindromic Repeat (CRISPR) associated endonuclease and a guide RNA sequence complementary to one or more target nucleic acid sequences in a retrovirus genome.
Claims (4)
1. A method of inactivating a viral deoxyribonucleic acid (DNA) sequence of a viral genome in a cell, the method comprising:
(a) cutting the viral DNA sequence at a first target sequence using a CRISPR-Cas targeted to the first target sequence by a first guide ribonucleic acid (gRNA);
(b) cutting the viral DNA sequence at a second target sequence using a CRISPR-Cas targeted to the second target sequence by a second gRNA, wherein the first target sequence and the second target sequence are different; and
wherein the method results in inactivating 64% to 96% of the viral DNA sequence in the cell and excising the viral DNA sequence between the first target sequence and the second target sequence from the viral genome in the cell.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 17, 2022
From: KHALILI, KAMEL; HU, WENHUI; ZHANG, YONGGANG
To: TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Reel/Frame 061816/0465 →
Continuity (5)
Continuation
15578372
Provisional Application
62308320
· Mar 15, 2016
Provisional Application
62169633
· Jun 2, 2015
Provisional Application
62169384
· Jun 1, 2015
References Cited (286)
US 5034506A
· Summerton et al.
· 1991
[cited by applicant]
US 8697359B1
· Zhang
· 2014
[cited by applicant]
US 8771945B1
· Zhang
· 2014
[cited by applicant]
US 8795965B2
· Zhang
· 2014
[cited by applicant]
US 8865406B2
· Zhang et al.
· 2014
[cited by applicant]
US 8871445B2
· Cong et al.
· 2014
[cited by applicant]
US 8889356B2
· Zhang
· 2014
[cited by applicant]
US 8889418B2
· Zhang et al.
· 2014
[cited by applicant]
US 8895308B1
· Zhang et al.
· 2014
[cited by applicant]
US 8906616B2
· Zhang et al.
· 2014
[cited by applicant]
US 8932814B2
· Cong et al.
· 2015
[cited by applicant]
US 8945839B2
· Zhang
· 2015
[cited by applicant]
US 8993233B2
· Zhang et al.
· 2015
[cited by applicant]
US 8999641B2
· Zhang et al.
· 2015
[cited by applicant]
US 9023649B2
· Mali et al.
· 2015
[cited by applicant]
US 9068179B1
· Liu et al.
· 2015
[cited by applicant]
US 9074199B1
· Chavez et al.
· 2015
[cited by applicant]
US 9163284B2
· Liu et al.
· 2015
[cited by applicant]
US 9228207B2
· Liu et al.
· 2016
[cited by applicant]
US 9260723B2
· Mali et al.
· 2016
[cited by applicant]
US 9267135B2
· Church et al.
· 2016
[cited by applicant]
US 9322037B2
· Liu et al.
· 2016
[cited by applicant]
US 9340799B2
· Liu et al.
· 2016
[cited by applicant]
US 9340800B2
· Liu et al.
· 2016
[cited by applicant]
US 9388430B2
· Liu et al.
· 2016
[cited by applicant]
US 9526784B2
· Liu et al.
· 2016
[cited by applicant]
US 9587252B2
· Church et al.
· 2017
[cited by applicant]
US 9737604B2
· Liu et al.
· 2017
[cited by applicant]
US 9822372B2
· Zhang et al.
· 2017
[cited by applicant]
US 9840699B2
· Liu et al.
· 2017
[cited by applicant]
US 9840713B2
· Zhang
· 2017
[cited by applicant]
US 9925248B2
· Khalili et al.
· 2018
[cited by applicant]
US 9925425B2
· Ladd et al.
· 2018
[cited by applicant]
US 9970024B2
· Church et al.
· 2018
[cited by applicant]
US 9981020B2
· Khalili et al.
· 2018
[cited by applicant]
US 9999671B2
· Liu et al.
· 2018
[cited by applicant]
US 20140342456A1
· Mali et al.
· 2014
[cited by applicant]
US 20140356956A1
· Church et al.
· 2014
[cited by applicant]
US 20150232833A1
· Mali et al.
· 2015
[cited by applicant]
US 20150232882A1
· Zhang et al.
· 2015
[cited by applicant]
US 20150247150A1
· Zhang et al.
· 2015
[cited by applicant]
US 20150291965A1
· Zhang et al.
· 2015
[cited by applicant]
US 20160153004A1
· Zhang et al.
· 2016
[cited by applicant]
US 20160281072A1
· Zhang
· 2016
[cited by applicant]
US 20160340662A1
· Zhang et al.
· 2016
[cited by applicant]
US 20170044569A9
· Church et al.
· 2017
[cited by applicant]
US 20170152528A1
· Zhang
· 2017
[cited by applicant]
US 20170198269A1
· Zhang et al.
· 2017
[cited by applicant]
US 20180000970A1
· Roehm et al.
· 2018
[cited by applicant]
US 20180169193A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180169195A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180200343A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180207243A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180208914A1
· Malcolm et al.
· 2018
[cited by applicant]
US 20180214521A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180221458A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180228874A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180228875A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180228876A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180236041A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180236043A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180236044A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180236045A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180236046A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180236103A1
· Friedland et al.
· 2018
[cited by applicant]
US 20180303915A1
· Khalili et al.
· 2018
[cited by applicant]
US 20180327756A1
· Zhang et al.
· 2018
[cited by applicant]
US 20180355375A1
· Zhang et al.
· 2018
[cited by applicant]
US 20190017058A1
· Zhang et al.
· 2019
[cited by applicant]
US 20190032057A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190083656A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190085326A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190093091A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190093092A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190153476A1
· Zhang
· 2019
[cited by applicant]
US 20190256844A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190365862A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190367910A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190367924A1
· Khalili et al.
· 2019
[cited by applicant]
US 20190390204A1
· Zhang et al.
· 2019
[cited by applicant]
US 20200032278A1
· Zhang et al.
· 2020
[cited by applicant]
US 20200063147A1
· Zhang et al.
· 2020
[cited by applicant]
US 20200080094A1
· Zhang et al.
· 2020
[cited by applicant]
US 20200299732A1
· Church et al.
· 2020
[cited by applicant]
US 20200318123A1
· Zhang
· 2020
[cited by applicant]
US 20200323984A1
· Liu et al.
· 2020
[cited by applicant]
US 20200354742A1
· Zhang et al.
· 2020
[cited by applicant]
US 20200392487A1
· Khalili et al.
· 2020
[cited by applicant]
US 20210079407A1
· Zhang
· 2021
[cited by applicant]
US 20210147879A1
· Byrne et al.
· 2021
[cited by applicant]
US 20210292794A1
· Zhang et al.
· 2021
[cited by applicant]
US 20210315994A1
· Liu et al.
· 2021
[cited by applicant]
US 20210361779A1
· Zhang et al.
· 2021
[cited by applicant]
US 20210366572A1
· Zhang et al.
· 2021
[cited by applicant]
US 20220135985A1
· Zhang et al.
· 2022
[cited by applicant]
US 20230340505A1
· Zhang
· 2023
[cited by applicant]
US 20230374527A1
· Zhang
· 2023
[cited by applicant]
US 20230399662A1
· Zhang
· 2023
[cited by applicant]
US 20240035048A1
· Zhang
· 2024
[cited by applicant]
US 20240117365A1
· Zhang
· 2024
[cited by applicant]
US 20240175057A1
· Church et al.
· 2024
[cited by applicant]
US 20240182913A1
· Zhang
· 2024
[cited by applicant]
US 20240209359A1
· Zhang et al.
· 2024
[cited by applicant]
CN 103923911A
· 2014
[cited by applicant]
CN 104480144A
· 2015
[cited by applicant]
CN 104726449
· 2015
[cited by applicant]
WO 2014165349A1
· 2014
[cited by applicant]
WO 2015031775A1
· 2015
[cited by applicant]
WO 2016196539A2
· 2016
[cited by applicant]
Scott, “The zinc finger nuclese monopoly” 23(8) Nature Biotechnology 915-918 (Year: 2005).
[cited by examiner]
Mussolino et al., “Tale nucleases: tailored genome engineering made easy” 23 Current Opinion in Biotechnology 644-650 (Year: 2012).
[cited by examiner]
Qu et al., “Zinc finger nuclease: a new approach for excising HIV-1 proviral DNA from infected human T cells” 41 Molecular Biology Reports 5819-5827 (Year: 2014).
[cited by examiner]
Gaj et al., “ZFN, TALEN, and CRISPR/Cas-based method for genome editing” 31(7) Trends in Biotechnology 397-405 (Year: 2013).
[cited by examiner]
Bassett et al. (Jan. 2014) “CRISPR/Cas9 and Genome Editing in
[cited by applicant]
Brinkman et al. (Dec. 2014) “Easy Quantitative Assessment of Genome Editing by Sequence Trace Decomposition”, Nucleic Acids Research, e168, 42(22):08 pages.
[cited by applicant]
Carrington et al. (Dec. 2015) “CRISPR-STAT: an easy and reliable PCR-based method to evaluate target-specific sgRNA activity”, Nucleic Acids Research, e157, 43(22):08 pages.
[cited by applicant]
Christensen et al. (1998) “A Novel Class of Oligonucleotide Analogues Containing 2'-O,3'-C-Linked [3.2.0] Bicycloarabinonucleoside Monomers: Synthesis, Thermal Affinity Studies, and Molecular Modeling”, Journal of the A…
[cited by applicant]
Dahlem et al. (Aug. 16, 2012) “Simple Methods for Generating and Detecting Locus-Specific Mutations Induced with TALENs in the Zebrafish Genome”, PLoS One, 8(8):15 pages.
[cited by applicant]
Dampier et al. (Oct. 2014) “HIV Excision Utilizing CRISPR/Cas9 Technology: Attacking the Proviral Quasispecies in Reservoirs to Achieve a Cure”, MOJ Immunology, 1(4):10 pages.
[cited by applicant]
De Mesmaeker et al. (Sep. 1995) “Antisense Oligonucleotides”, Accounts of Chemical Research, 28 (9):366-374.
[cited by applicant]
Doench et al. (Dec. 2014) “Rational Design of Highly Active sgRNAs for CRISPR-Cas9-Mediated Gene Inactivation”, Nature Biotechnology, 32(12):17 pages.
[cited by applicant]
Ebina et al. (Aug. 26, 2013) “Harnessing the CRISPR/Cas9 System to Disrupt Latent HIV-1 Provirus”, Scientific Reports, 3(2510):1-7.
[cited by applicant]
Felgner et al. (1989) “Cationic Liposome-Mediated Transfection”, Bethesda Research Laboratories Focus, 11 (2):21-25.
[cited by applicant]
Freier et al. (1997) “The Ups and Downs of Nucleic Acid Duplex Stability: Structure-Stability Studies on Chemically-Modified DNA:RNA Duplexes”, Nucleic Acids Research, 25(22):4429-4443.
[cited by applicant]
Frock et al. (Feb. 2015) “Genome-Wide Detection of DNA Double-Stranded Breaks Induced by Engineered Nucleases”, Nature Biotechnology, 33(2):11 pages.
[cited by applicant]
Gagnon et al.(Aug. 2014) “Efficient Mutagenesis by Cas9 ProteinMediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs”, PLoS ONE, 9(5):8 pages.
[cited by applicant]
Gebeyehu et al. (Jun. 11, 1987) “Novel Biotinylated Nucleotide-Analogs for Labeling and Colorimetric Detection of DNA”, Nucleic Acids Research, 15(11):4513-4534.
[cited by applicant]
Güell et al. (Oct. 15, 2014) “Genome Editing Assessment Using CRISPR Genome Analyzer (CRISPR-GA)”, Bioinformatics, 30(20):2968-2970.
[cited by applicant]
Herdewin Piet, (Jul. 8, 2000) “Heterocyclic Modifications of Oligonucleotides and Antisense Technology”, Antisense and Nucleic Acid Drug Development, 10(4):297-310.
[cited by applicant]
Hu et al. (Jan. 1, 2015) “Generation of a Stable Packaging Cell Line Producing High-Titer PPT-Deleted Integration-Deficient Lentiviral Vectors”, Molecular Therapy—Methods & Clinical Development, 2(15025):10 pages.
[cited by applicant]
Jadlowsky et al. (Jun. 2014) “Negative Elongation Factor Is Required for the Maintenance of Proviral Latency but Does Not Induce Promoter-Proximal Pausing of RNA Polymerase Il on the HIV Long Terminal Repeat”, Molecular…
[cited by applicant]
Kabanov et al. (Jan. 1, 1990) “A New Class of Antivirals: Antisense Oligonucleotides Combined with a Hydrophobic Substituent Effectively Inhibit Influenza Virus Reproduction and Synthesis of Virus-Specific Proteins in M…
[cited by applicant]
Kaminski et al. (Aug. 2016) “Excision of HIV-1 DNA by Gene Editing: A Proof-of-Concept in Vivo Study”, Gene Therapy, 23(8-9):13 pages.
[cited by applicant]
Khalili et al. (Jun. 2015) “Genome Editing Strategies: Potential Tools for Eradicating HIV-1/AIDS”, Journal of NeuroVirology, 21(3):310-321.
[cited by applicant]
Kim et al. (2014) “Genotyping with CRISPR-Cas-derived RNA-guided endonucleases”, Nature Communications, 5 (3157):08 pages.
[cited by applicant]
Kopp et al. (Mar. 1992) “Progressive Glomerulosclerosis and Enhanced Renal Accumulation of Basement Membrane Components in Mice Transgenic for Human Immunodeficiency Virus Type 1 Genes”, PNAS, 89 (5):1577-1581.
[cited by applicant]
Kornberg et al. (1980) “DNA Replication”, San Francisco: W. H. Freeman and Co., 75-77.
[cited by applicant]
Letsinger et al. (1989) “Cholesteryl-Conjugated Oligonucleotides: Synthesis, Properties, and Activity as Inhibitors of Replication of Human Immunodeficiency Virus in Cell Culture”, Proceedings of the National Academy of…
[cited by applicant]
Liao et al. (Mar. 10, 2015) “Use of the CRISPR/Cas9 System as an Intracellular Defense against HIV-1 Infection in Human Cells”, Nature Communications, 6(6413):10 pages.
[cited by applicant]
Liu et al. (Nov. 15, 2015) “Crispr-Era: A Comprehensive Design Tool for CRISPR-Mediated Gene Editing, Repression and Activation”, Bioinformatics, 31(22):3676-3678.
[cited by applicant]
Liu et al. (Oct. 2014) “Integrase-Deficient Lentivirus: Opportunities and Challenges for Human Gene Therapy”, Current Gene Therapy, 14(5):352-364.
[cited by applicant]
Madabhushi et al. (Jun. 18, 2015) “Activity-Induced DNA Breaks Govern the Expression of Neuronal Early-Response Genes”, Cell, 161(7):1592-1605.
[cited by applicant]
Mali et al. (Sep. 2013) “CAS9 Transcriptional Activators for Target Specificity Screening and Paired Nickases for Cooperative Genome Engineering”, Nature Biotechnology, 31(9):17 pages.
[cited by applicant]
Manjunath et al. (Nov. 14, 2013) “Newer Gene Editing Technologies toward HIV Gene Therapy”, Viruses, 5 (11):2748-2766.
[cited by applicant]
Mannino et al. (Jul. 1, 1988) “Liposome Mediated Gene Transfer”, BioTechniques, 6(7):682-690.
[cited by applicant]
Manoharan M. (Dec. 10, 1999) “2'-Carbohydrate Modifications in Antisense Oligonucleotide Therapy: Importance of Conformation, Configuration and Conjugation”, Biochimica et Biophysica Acta—Gene Structure and Expression, …
[cited by applicant]
Manoharan et al. (Oct. 28, 1992) “Chemical Modifications to Improve Uptake and Bioavailability of Antisense Oligonucleotides”, Annals of the New York Academy of Sciences banner, Antisense Strategies, 660(1):306-309.
[cited by applicant]
Manoharan et al. (Apr. 21, 1994) “Cholic Acid-Oligonucleotide Conjugates for Antisense Applications”, Bioorganic & Medicinal Chemistry Letters, 4(8):1053-1060.
[cited by applicant]
Manoharan et al. (Dec. 1993) “Introduction of a Lipophilic Thioether Tether in the Minor Groove of Nucleic Acids for Antisense Applications”, Bioorganic & Medicinal Chemistry Letters, 3(12):2765-2770.
[cited by applicant]
Manoharan et al. (May 22, 1995) “Lipidic Nucleic Acids”, Tetrahedron Letters, 36(21):3651-3654.
[cited by applicant]
Manoharan et al. (1995) “Oligonucleotide Conjugates: Alteration of the Pharmacokinetic Properties of Antisense Agents”, Nucleosides and Nucleotides, 14(3-5):969-973.
[cited by applicant]
Maurer et al. (1989) “Cationic Liposome-Mediated Transfection of Primary Cultures of Rat Pituitary Cells”, Focus, 11 (2):25-27.
[cited by applicant]
Nielsen et al. (Dec. 6, 1991) “Sequence-Selective Recognition of DNA by Strand Displacement with a Thymine-Substituted Polyamide”, Science, 254(5037):1497-1500.
[cited by applicant]
Oberhauser et al. (Feb. 11, 1992) “Effective Incorporation of 2'-O-Methyl-Oligoribonucleotides into Liposomes and Enhanced Cell Association through Modification with Thiocholesterol”, Nucleic Acids Research, 20(3):533-5…
[cited by applicant]
Peng et al. (Oct. 2015) “CRISPR/Cas9-based tools for targeted genome editing and replication control of HBV”, Virologica Sinica, 30(5):317-325.
[cited by applicant]
Qiu P et al. (Apr. 2004) “Mutation Detection using Surveyor Nuclease”, Biotechniques, 36(4):702-707.
[cited by applicant]
Ramanan et al. (Dec. 2015) “CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus”, Scientific Reports, 5:09 pages.
[cited by applicant]
Ran et al. (Sep. 12, 2013) “Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity”, Cell, 154(6):1380-1389.
[cited by applicant]
Ran et al. (Apr. 9, 2015) “In Vivo Genome Editing Using
[cited by applicant]
Saison-Behmoaras et al. (1991) “Short Modified Antisense Oligonucleotides Directed Against Ha-ras Point Mutation Induce Selective Cleavage of the mRNA and Inhibit T24 Cells Proliferation”, EMBO Journal, 10(5):1111-1118.
[cited by applicant]
Sander et al. (Aug. 5, 2011) “Targeted Gene Disruption in Somatic Zebrafish Cells Using Engineered TALENs”, Nature Biotechnology, 29(8):6 pages.
[cited by applicant]
Sanghvi et al. (1993) “Antisense Research and Applications”, Stanley T. Crooke, Bernard Lebleu eds., CRC Press, Boca Raton, 276-278.
[cited by applicant]
Scheit Karlh., (1980) “Nucleotide Analogs—Synthesis and Biological Function”, FEBS Letters, 122(2):01 page.
[cited by applicant]
Shea et al. (Jul. 11, 1990) “Synthesis, Hybridization Properties and Antiviral Activity of Lipid-Oligodeoxynucleotide Conjugates”, Nucleic Acids Research, 18(13):3777-3783.
[cited by applicant]
Smith et al. (Jul. 2014) “Whole-Genome Sequencing Analysis Reveals High Specificity of CRISPR/Cas9 and TALEN-Based Genome Editing in Human iPSCs”, Cell Stem Cell, 15(1):3 pages.
[cited by applicant]
Song et al. (Oct. 2015) “Visualization and Quantification of Simian Immunodeficiency Virus-Infected Cells using Non-Invasive Molecular Imaging”, Journal of General Virology, 96:3131-3142.
[cited by applicant]
Stone et al. (May 2013) “Targeted Gene Disruption to Cure HIV”, Current Opinion in HIV and AIDS, 8(3):12 pages.
[cited by applicant]
Svinarchuk et al.(1993) “Inhibition of HIV Proliferation in MT-4 Cells by Antisense Oligonucleotide Conjugated to Lipophilic Groups”, Biochimie, 75(1-2):49-54.
[cited by applicant]
Toulme Jean-Jacques, (Jan. 1, 2001) “New Candidates for True Antisense”, Nature Biotechnology, 19 (1):17-18.
[cited by applicant]
Tsai et al. (Jun. 2014) “Dimeric CRISPR RNA-Guided Fokl Nucleases for Highly Specific Genome Editing”, Nature Biotechnology, 32(6):569-576.
[cited by applicant]
Uhlmann E. (Mar. 2000) “Recent Advances in Medicinal Chemistry of Antisense Oligonucleotides”, Current Opinion in Drug Discovery & Development, 3(2):203-213.
[cited by applicant]
Veres et al. (Jul. 3, 2014) “Low Incidence of Off-Target Mutations in Individual CRISPR-Cas9 and TALEN Targeted Human Stem Cell Clones Detected by Whole-Genome Sequencing”, Cell Stem Cell, 15:27-30.
[cited by applicant]
Wang et al. (Dec. 26, 2014) “Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection”, PLoS One, e115987, 9(12):26 pages.
[cited by applicant]
Wyvekens et al. (Jul. 2015) “Dimeric CRISPR RNA-Guided Fokl-dCas9 Nucleases Directed by Truncated gRNAs for Highly Specific Genome Editing”, Human Gene Therapy, 26(7):425-431.
[cited by applicant]
Yang et al. (Nov. 26, 2014) “Targeted and Genome-Wide Sequencing Reveal Single Nucleotide Variations Impacting Specificity of Cas9 in Human Stem Cells”, Nature Communications, 5(5507):06 pages.
[cited by applicant]
Yu et al. (Jun. 5, 2014) “A PCR Based Protocol for Detecting Indel Mutations Induced by TALENs and CRISPR/Cas9 in Zebrafish”, PLoS ONE, e98282, 9(6):07 pages.
[cited by applicant]
Yuen et al. (Mar. 2015) “CRISPR/Cas9-Mediated Genome Editing of Epstein-Barr Virus in Human Cells”, Journal of General Virology, 96(Pt. 3):626-636.
[cited by applicant]
Zuckermann et al. (2015) “Somatic CRISPR/Cas9-Mediated Tumour Suppressor Disruption Enables Versatile Brain Tumour Modelling”, Nature Communications, 6(7391):09 pages.
[cited by applicant]
Wei et al. (2014) “Application of CRISPR/Cas9 System for Gene Regulation”, Acta Veterinaria et Zootechnica Sinica, 45(9):1387-1392.
[cited by applicant]
Hu et al., “RNA-Directed Gene Editing Specifically Eradicates Latent and Prevents New HIV-1 Infection,” Proceedings of the National Academy of Sciences, 111:31, pp. 114612-11466, 2014.
[cited by applicant]
Wigdahl, “HIV Excision Utilizing CRISPR/Cas9 Technology: Attacking the proviral Quasispecies in Reservoirs to Achieve a Cure,” MOJ Immunology, 1:4, pp. 1-10, 2015.
[cited by applicant]
Boerner, et al., “AAV Vector-Mediated CRISPR attaches on Proviral HIV-1 Dna for Purging of Cellular Reservoirs,” Molecular Therapy, vol. 23:1, 1 pages 2015.
[cited by applicant]
Supplementary European Search Report from EP Application No. 16804274, dated Dec. 13, 2018, pp. 1-3.
[cited by applicant]
Saayman et al., The Therapeutic Application of CRISPR/Cas9 Technologies for HIV. Expert Opin Biol Ther ePub Apr. 12, 2015, vol. 15 No. 6 pp. 819-830. Especially entire article (review).
[cited by applicant]
International Search Report issued in corresponding International Application No. PCT/US2016/035141, Dec. 28, 2016, 6 pages.
[cited by applicant]
Written Opinion of the International Searching Authority issued in corresponding International Application No. PCT/US2016/035141, Dec. 28, 2016, 7 pages.
[cited by applicant]
Sorek et al., “CRISPR-Mediated Adaptive Immune Systems in Bacteria and Archaea”, 82 Annual Review of Biochemistry, pp. 237-266, 2013.
[cited by applicant]
Hu et al., “RNA-Directed Gene Editing Specifically Eradicates Latent and Prevents New HIV-1 Infection,” 111:31, Proceedings of the National Academy of Sciences, 11461-11466, Aug. 5, 2014.
[cited by applicant]
Koonin et al., “Diversity, Classification and Evolution of CRISPR-Cas Systems,” 37 Current Opinion in Microbiology, pp. 67-78, 2017.
[cited by applicant]
Brander et al., “Lack of Strong Immune Selection Pressure by the Immunodominant, HLA-A*0201-Restricted Cytotoxic T Lymphocyte Response in Chronic Human Immunodeficiency Virus-1 Infection,” Journal of Clinical Investigat…
[cited by applicant]
Chang et al., (2013) Genome Editing with RNA-Guided Cas9 nuclease in zebrafish embryos, Cell Research 23: 465-472.
[cited by applicant]
Cong et al., (2013) Multiplex Genome Engineering Using CRISPR/Cas Systems, Science 3;339(6121): 819-823.
[cited by applicant]
Esvelt et al., (2013) Orthogonal Cas9 proteins for RNA-guided gene regulation and editing, Author manuscript, Published in final edited form as: Nature Methods 10(11):1116-1121.
[cited by applicant]
Gilbert et al., (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes, Cell Research, 154:442-451.
[cited by applicant]
Horvath et al., (2010) CRISPR/Cas, the immune system of bacteria and archaea, Science, 327: 167-170.
[cited by applicant]
Hsu et al., (2013) DNA targeting specificity of RNA-guided Cas9 nucleases, Nature Biotechnology, 31, 827-832.
[cited by applicant]
Hwang et al., (2013) Efficient In Vivo Genome Editing Using RNA-Guided Nucleases, Author manuscript, Published in final edited form as: “Efficient genome editing in zebrafish using a CRISPR-Cas system,” Nature Biotechno…
[cited by applicant]
Jiang et al., (2015) CRISPR-Cas: New Tools for Genetic Manipulations from Bacterial Immunity Systems, Annu Rev Microbiol. 2015:69:209-28.
[cited by applicant]
Jinek et al., (2012) A programmable dual RNA-guided DNA endonuclease in adaptive bacterial immunity, Science 337 (6089): 816-821.
[cited by applicant]
Jinek et al., (2013) RNA-programmed genome editing in human cells, eLife, 2(e0047): 1-9.
[cited by applicant]
Kleinstiver et al., (2016) High fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects Author manuscript, Published in final edited form as: Nature, 529 (7587): 490-495.
[cited by applicant]
Lin et al., (2014) The CRISPR/Cas9 system facilitates clearance of the intrahepatic HBV templates in vivo, Molecular Therapy—Nucleic Acids (2014), 3: e186, pp. 1-7.
[cited by applicant]
Maggio et al., (2014) Adenoviral Vector Delivery of RNA-Guided CRISPR/Cas9 Nuclease Complexes Induces Targeted Mutagenesis in a Diverse Array of Human Cells, Scientific Reports, vol. 4, No. 5105.
[cited by applicant]
Mali et al., (2013) RNA-guided human genome engineering via Cas9, Science, 339(6121): 823-826.
[cited by applicant]
Ramalingam et al., (2013) A CRISPR way to engineer the human genome, Genome Biology, 14(107).
[cited by applicant]
Schiffer et al., (2012) Targeted DNA mutagenesis for the cure of chronic viral infections, Journal of Virology 86(17): 8920-8936.
[cited by applicant]
Silva et al., (2011) Meganucleases and Other Tools for Targeted Genome Editing: Perspectives and Challenges for Gene Therapy, Curr Gene Ther 11(1): 11-27.
[cited by applicant]
Wang et al., (Mar. 2016) CRISPR-Cas9 can inhibit HIV-1 Replication but NHEJ repair facilitates virus escape, Molecular therapy, 24(3): 522-526.
[cited by applicant]
Xie et al., (2014) sgRNAcas9: a software package for designing CRISPR sgRNA and evaluating potential off-target cleavage sites, PLOS One 9.6 (2014): e100448.
[cited by applicant]
Yin et al., (2016) Functional Screening of Guide RNAs targeting the regulatory and structural HIV-1 viral genome for a cure of AIDS, AIDS, 30(8): 1163-1174.
[cited by applicant]