Granted Patent
B2
US 12,630,841 · App. 17/599,750 · Granted May 19, 2026
Adeno-associated virus with engineered capsid
Assignee:
Tenaya Therapeutics, Inc.
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Abstract
The present disclosure provides recombinant adeno-associated virus (rAAV) virions with an engineered capsid protein identified using a high-throughput sequencing screen or rational design. In particular, the disclosure provides AAV5 virions and capsid proteins with increased transduction efficiency in cardiac cells, increased cell-type selectivity, and/or other desirable properties.
Claims (12)
1 . A recombinant adeno-associated virus (rAAV) virion, comprising:
a) an AAV5 capsid protein, wherein the capsid protein comprises two or more substitutions selected from S651A or S651V; T578A or T578V; and/or T582A or T582V in a parental AAV5 capsid; and
b) a heterologous nucleic acid comprising a nucleotide sequence encoding a gene product.
2 . The rAAV virion of claim 1 , wherein the AAV5 capsid protein comprises T582A and S651A substitutions.
3 . The rAAV virion of claim 1 , wherein the AAV5 capsid protein comprises S651A, T578A, and T582A substitutions.
4 . The rAAV virion of claim 1 , wherein the AAV5 capsid protein comprises a sequence having at least 95% identity, at least 98% identity, or at least 99% identity to the sequence of SEQ ID NO: 73.
5 . A pharmaceutical composition comprising the rAAV virion of claim 1 .
6 . An AAV5 capsid protein comprising two or more substitutions selected from S651A or S651V; T578A or T578V; and/or T582A or T582V in a parental AAV5 capsid.
7 . The AAV5 capsid protein of claim 6 , wherein the capsid protein comprises T582A and S651A substitutions.
8 . The AAV5 capsid protein of claim 6 , wherein the capsid protein comprises S651A, T578A, and T582A substitutions.
9 . The AAV5 capsid protein of claim 6 , wherein the capsid protein comprises a sequence having at least 90% identity, at least 95% identity, at least 98% identity, or at least 99% identity to the sequence of SEQ ID NO: 73.
10 . A polynucleotide encoding the AAV5 capsid protein of claim 6 .
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 29, 2021
From: REID, CHRISTOPHER A.
To: TENAYA THERAPEUTICS, INC.
Reel/Frame 057641/0768 →
Continuity (3)
Provisional Application
62984197
· Mar 2, 2020
Provisional Application
62827576
· Apr 1, 2019
References Cited (350)
US 4683195A
· Mullis et al.
· 1987
[cited by applicant]
US 4683202A
· Mullis
· 1987
[cited by applicant]
US 4797368A
· Carter et al.
· 1989
[cited by applicant]
US 4962091A
· Eppstein et al.
· 1990
[cited by applicant]
US 5139941A
· Muzyczka et al.
· 1992
[cited by applicant]
US 5449614A
· Danos et al.
· 1995
[cited by applicant]
US 5591624A
· Barber et al.
· 1997
[cited by applicant]
US 5817491A
· Yee et al.
· 1998
[cited by applicant]
US 5834256A
· Finer et al.
· 1998
[cited by applicant]
US 5925565A
· Berlioz et al.
· 1999
[cited by applicant]
US 5928906A
· Koster et al.
· 1999
[cited by applicant]
US 5935819A
· Eichner et al.
· 1999
[cited by applicant]
US 5994136A
· Naldini et al.
· 1999
[cited by applicant]
US 6013516A
· Verma et al.
· 2000
[cited by applicant]
US 6156303A
· Russell et al.
· 2000
[cited by applicant]
US 6306434B1
· Hong, II et al.
· 2001
[cited by applicant]
US 6872528B2
· Klatzmann et al.
· 2005
[cited by applicant]
US 6910434B2
· Lundgren
· 2005
[cited by applicant]
US 6962815B2
· Bartlett
· 2005
[cited by applicant]
US 6984517B1
· Chiorini et al.
· 2006
[cited by applicant]
US 6995009B1
· Kitamura et al.
· 2006
[cited by applicant]
US 7070994B2
· Barber et al.
· 2006
[cited by applicant]
US 7091029B2
· Hwang
· 2006
[cited by applicant]
US 7105345B2
· Wilson et al.
· 2006
[cited by applicant]
US 7198951B2
· Gao et al.
· 2007
[cited by applicant]
US 7259151B2
· Arbetman et al.
· 2007
[cited by applicant]
US 7718424B2
· Chiorini et al.
· 2010
[cited by applicant]
US 7790449B2
· Gao et al.
· 2010
[cited by applicant]
US 7867484B2
· Samulski et al.
· 2011
[cited by applicant]
US 7906111B2
· Wilson et al.
· 2011
[cited by applicant]
US 8119119B2
· Mallet et al.
· 2012
[cited by applicant]
US 8524446B2
· Gao et al.
· 2013
[cited by applicant]
US 8679837B2
· Zolotukhin et al.
· 2014
[cited by applicant]
US 8784799B2
· Samulski et al.
· 2014
[cited by applicant]
US 8906675B2
· Gao et al.
· 2014
[cited by applicant]
US 8999678B2
· Vandenberghe et al.
· 2015
[cited by applicant]
US 9169494B2
· Hewitt et al.
· 2015
[cited by applicant]
US 9233131B2
· Schaffer et al.
· 2016
[cited by applicant]
US 9434928B2
· Mendell et al.
· 2016
[cited by applicant]
US 9441206B2
· Grieger et al.
· 2016
[cited by applicant]
US 9441244B2
· Schaffer et al.
· 2016
[cited by applicant]
US 9447433B2
· Hirsch et al.
· 2016
[cited by applicant]
US 9737618B2
· Wilson et al.
· 2017
[cited by applicant]
US 9783824B2
· Kay et al.
· 2017
[cited by applicant]
US 9790472B2
· Gao et al.
· 2017
[cited by applicant]
US 20030022870A1
· Dzau et al.
· 2003
[cited by applicant]
US 20030138772A1
· Gao
· 2003
[cited by examiner]
US 20070161031A1
· Trinklein et al.
· 2007
[cited by applicant]
US 20110104679A1
· DeAngelis et al.
· 2011
[cited by applicant]
US 20110296544A1
· Domon et al.
· 2011
[cited by applicant]
US 20160237430A1
· Seidman et al.
· 2016
[cited by applicant]
US 20180296703A1
· Feldman et al.
· 2018
[cited by applicant]
US 20180305689A1
· Saetrom et al.
· 2018
[cited by applicant]
US 20190169237A1
· Schaffer et al.
· 2019
[cited by applicant]
US 20210077552A1
· Schaffer et al.
· 2021
[cited by applicant]
US 20210147873A1
· Zhu et al.
· 2021
[cited by applicant]
US 20210284699A1
· Gradinaru et al.
· 2021
[cited by applicant]
US 20220064675A1
· McCoy et al.
· 2022
[cited by applicant]
US 20220106612A1
· Linden
· 2022
[cited by applicant]
US 20220168447A1
· Herzog et al.
· 2022
[cited by applicant]
US 20220177881A1
· Momen-Heravi
· 2022
[cited by applicant]
US 20220249697A1
· Liu et al.
· 2022
[cited by applicant]
US 20220273818A1
· Maeder et al.
· 2022
[cited by applicant]
US 20220372512A1
· Lisowski et al.
· 2022
[cited by applicant]
US 20220403414A1
· Ji et al.
· 2022
[cited by applicant]
US 20230041648A1
· Yang et al.
· 2023
[cited by applicant]
US 20230051968A1
· Yang et al.
· 2023
[cited by applicant]
US 20230056066A1
· Yang et al.
· 2023
[cited by applicant]
CA 3031026A1
· 2018
[cited by applicant]
CN 109476707A
· 2019
[cited by applicant]
EP 3387137B1
· 2021
[cited by applicant]
EP 3941929A1
· 2022
[cited by applicant]
EP 3959226A2
· 2022
[cited by applicant]
EP 4019642A1
· 2022
[cited by applicant]
EP 4045664A1
· 2022
[cited by applicant]
EP 3856913A4
· 2022
[cited by applicant]
JP 2016513477A
· 2016
[cited by applicant]
WO WO9303769A1
· 1993
[cited by applicant]
WO WO9309239A1
· 1993
[cited by applicant]
WO WO9319191A1
· 1993
[cited by applicant]
WO WO9407529A1
· 1994
[cited by applicant]
WO WO9412649A2
· 1994
[cited by applicant]
WO WO9428938A1
· 1994
[cited by applicant]
WO WO9500655A1
· 1995
[cited by applicant]
WO WO9511984A2
· 1995
[cited by applicant]
WO WO9513392A1
· 1995
[cited by applicant]
WO WO9811244A2
· 1998
[cited by applicant]
WO WO9961601A2
· 1999
[cited by applicant]
WO WO0028061A2
· 2000
[cited by applicant]
WO WO0111034A2
· 2001
[cited by applicant]
WO WO0183692A2
· 2001
[cited by applicant]
WO WO0192551A2
· 2001
[cited by applicant]
WO WO03042361A2
· 2003
[cited by applicant]
WO WO2007078599A2
· 2007
[cited by applicant]
WO WO2008021290A2
· 2008
[cited by applicant]
WO WO2008024998A2
· 2008
[cited by applicant]
WO WO2009104964A1
· 2009
[cited by applicant]
WO WO2010129021A1
· 2010
[cited by applicant]
WO WO2011020710A2
· 2011
[cited by applicant]
WO WO2012145601A2
· 2012
[cited by applicant]
WO WO2013063379A1
· 2013
[cited by applicant]
WO WO2014144229A1
· 2014
[cited by applicant]
WO WO2015031686A1
· 2015
[cited by applicant]
WO WO2015162161A1
· 2015
[cited by applicant]
WO WO2016133917A1
· 2016
[cited by applicant]
WO 2016141078
· 2016
[cited by examiner]
WO WO2017075627A1
· 2017
[cited by applicant]
WO WO2017100671A1
· 2017
[cited by applicant]
WO WO2017173137A1
· 2017
[cited by applicant]
WO WO2017197355A2
· 2017
[cited by applicant]
WO WO2017201121A1
· 2017
[cited by applicant]
WO WO2018005546A1
· 2018
[cited by applicant]
WO WO2018222503A1
· 2018
[cited by applicant]
WO WO2019052057A1
· 2019
[cited by applicant]
WO WO2019060454A2
· 2019
[cited by applicant]
WO WO2019060619A1
· 2019
[cited by applicant]
WO WO2019195444A1
· 2019
[cited by applicant]
WO WO2019207132A1
· 2019
[cited by applicant]
WO WO2020047467A2
· 2020
[cited by applicant]
WO WO2020068990A1
· 2020
[cited by applicant]
WO WO2020152210A1
· 2020
[cited by applicant]
WO WO2020191300A1
· 2020
[cited by applicant]
WO WO2020193698A1
· 2020
[cited by applicant]
WO WO2020205889A1
· 2020
[cited by applicant]
WO WO2020219988A2
· 2020
[cited by applicant]
WO WO2020223279A1
· 2020
[cited by applicant]
WO WO2021034222A1
· 2021
[cited by applicant]
WO WO2021053222A1
· 2021
[cited by applicant]
WO WO2021073568A1
· 2021
[cited by applicant]
WO WO2021110995A1
· 2021
[cited by applicant]
WO WO2021127655A1
· 2021
[cited by applicant]
WO WO2021187380A1
· 2021
[cited by applicant]
WO WO2022031914A2
· 2022
[cited by applicant]
WO WO2022032226A1
· 2022
[cited by applicant]
WO WO2022038140A1
· 2022
[cited by applicant]
WO WO2022066898A2
· 2022
[cited by applicant]
WO WO2022074105A1
· 2022
[cited by applicant]
WO WO2022076648A1
· 2022
[cited by applicant]
WO WO2022079082A1
· 2022
[cited by applicant]
WO WO2022098765A1
· 2022
[cited by applicant]
WO WO2022119871A2
· 2022
[cited by applicant]
WO WO2022119974A1
· 2022
[cited by applicant]
WO WO2022119979A1
· 2022
[cited by applicant]
WO WO2022136655A1
· 2022
[cited by applicant]
WO WO2022173847A2
· 2022
[cited by applicant]
WO WO2022195074A2
· 2022
[cited by applicant]
WO WO2022200858A1
· 2022
[cited by applicant]
WO WO2022216574A1
· 2022
[cited by applicant]
WO WO2022217222A2
· 2022
[cited by applicant]
WO WO2022226263A1
· 2022
[cited by applicant]
WO WO2022229807A1
· 2022
[cited by applicant]
WO WO2023200736A2
· 2023
[cited by applicant]
WO WO2023200742A2
· 2023
[cited by applicant]
Bantel-Schaal et al. “Human Adeno-Associated Virus Type 5 Is Only Distantly Related to Other Known Primate Helper-Dependent Parvoviruses.” Journal of Virology, vol. 73, No. 2, pp. 939-947 (Feb. 1999).
[cited by applicant]
Chiorini et al. “Cloning and Characterization of Adeno-Associated Virus Type 5.” Journal of Virology, vol. 73, No. 2, pp. 1309-1319 (Feb. 1999).
[cited by applicant]
Chiorini et al. “Cloning of Adeno-Associated Virus Type 4 (AAV4) and Generation of Recombinant AAV4 Particles,” Journal of Virology, vol. 71, No. 9, pp. 6823-6833 (Sep. 1997).
[cited by applicant]
Gao et al., “A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse,” Circulation Research, 107: 1445-1453 (Dec. 2010), DOI: 10.1161/CIRCRESAHA.110.223925.
[cited by applicant]
Gao et al. “Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy” PNAS, vol. 99, No. 18, pp. 11854-11859 (Sep. 2002).
[cited by applicant]
GenBank Accession No. AAB95450, “capsid protein VP1 [Adeno-associated virus—6],” Jan. 12, 1998, 2 pages.
[cited by applicant]
GenBank Accession No. AAD13756, “capsid protein [adeno-associated virus 5],” Feb. 9, 1999, 2 pages.
[cited by applicant]
GenBank Accession No. AAS99264, “capsid protein VP1 [Adeno-associated virus 9],” Jun. 24, 2004, 2 pages.
[cited by applicant]
GenBank Accession No. AAT46337, “capsid protein [Adeno-associated virus 10],” Nov. 30, 2004, 2 pages.
[cited by applicant]
GenBank Accession No. AF043303, “Adeno-associated virus 2, complete genome,” May 20, 2010, 5 pages.
[cited by applicant]
GenBank Accession No. AF063497, “Adeno-associated virus 1, complete genome,” Apr. 27, 1999, 3 pages.
[cited by applicant]
GenBank Accession No. AF513851, “Adeno-associated virus 7 nonstructural protein and capsid protein genes, complete cds,” Sep. 5, 2002, 4 pages.
[cited by applicant]
GenBank Accession No. AF513852, “Adeno-associated virus 8 nonstructural protein and capsid protein genes, complete cds,” Sep. 5, 2002, 4 pages.
[cited by applicant]
GenBank Accession No. NC_001401, “Adeno-associated virus 2, complete genome,” Aug. 13, 2018, 10 pages.
[cited by applicant]
Genbank Accession No. NC_001729, “Adeno-associated virus—3, complete genome,” Aug. 13, 2018, 3 pages.
[cited by applicant]
GenBank Accession No. NC_001829, “adeno-associated Virus—4, complete genome,” Aug. 13, 2018, 5 pages.
[cited by applicant]
GenBank Accession No. NC-002077, “Adeno-associated virus—1, complete genome,” Aug. 13, 2018, 5 pages.
[cited by applicant]
GenBank Accession No. NC_006152, “Adeno-associated virus 5, complete genome,” Aug. 13, 2018, 5 pages.
[cited by applicant]
GenBank Accession No. NC_006261, “Adeno-associated virus—8, complete genome,” Aug. 13, 2018, 5 pages.
[cited by applicant]
GenBank Accession No. NP_044927, “capsid [Adeno-associated Virus—4],” Aug. 13, 2018, 3 pages.
[cited by applicant]
GenBank Accession No. NP_049542, “capsid protein [Adeno-associated virus—1],” Aug. 13, 2018, 2 pages.
[cited by applicant]
GenBank Accession No. U89790, “Adeno-associated virus 4, complete genome,” Aug. 21, 1997, 4 pages.
[cited by applicant]
GenBank Accession No. YP_077178, “capsid protein [Adeno-associated virus—7],” Aug. 13, 2018, 2 pages.
[cited by applicant]
GenBank Accession No. YP_077180, “capsid protein [Adeno-associated virus—8],” Aug. 13, 2018, 2 pages.
[cited by applicant]
Georg-Fries, B et al., “Analysis of proteins, helper dependence, and seroepidemiology of a new human parvovirus,” Virology, vol. 134, pp. 64-71 (1984).
[cited by applicant]
Govindasamy et al., “Structural Insights into Adeno-Associated Virus Serotype 5,” Journal of Virology, vol. 87, No. 20, pp. 11187-11199 (Oct. 2013).
[cited by applicant]
Govindasamy, L. et al., “Structurally Mapping the Diverse Phenotype of Adeno-Associated Virus Serotype 4,” Journal of Virology, vol. 80, No. 23, pp. 11556-11570 (Dec. 2006).
[cited by applicant]
Kyöstiö, S. R. M. et al., “Analysis of Adeno-Associated Virus (AAV) Wild-Type and Mutant Rep Proteins for Their Abilities to Negatively Regulate AAV p5 and p19 mRNA levels,” Journal of Virology, vol. 68, No. 5, pp. 2947…
[cited by applicant]
Marsic, D. et al., “Vector Design Tour de Force: Integrating Combinatorial and Rational Approaches to Derive Novel Adeno-associated Virus Variants,” Molecular Therapy, Nov. 2014, vol. 22, No. 11, pp. 1900-1909.
[cited by applicant]
McCarty, D.M., “Self-complementary AAV vectors; Advances and Applications,” Molecular Therapy, vol. 16, No. 10, pp. 1648-1656 (Oct. 2008).
[cited by applicant]
Mori, et al., “Two novel adeno-associated viruses from cynomolgus monkey: pseudotyping characterization of capsid protein,” Virology, 330, pp. 375-383 (2004).
[cited by applicant]
Muramatsu, et al., “Nucleotide Sequencing and Generation of an Infectious Clone of Adeno-Associated Virus 3,” Virology 221, pp. 208-217 (1996) Article No. 0367.
[cited by applicant]
Muzyczka, N. “Use of adeno-Associated Virus as a General Transduction Vector for Mammalian Cells,” Current Topics in Microbiology and Immunology 158:97-129 (1992).
[cited by applicant]
Nam et al. “Structure of Adeno-Associated Virus Serotype 8, a Gene Therapy Vector” Journal of Virology, vol. 81, No. 22, pp. 12260-12271 (Nov. 2007).
[cited by applicant]
Padron, E. et al. “Structure of Adeno-Associated Virus Type 4” Journal of Virology, vol. 79, No. 8, pp. 5047-5058 (Apr. 2005).
[cited by applicant]
Prasad, K. M., et al., “Characterization of the Rep78/Adeno-Associated Virus Complex,” Virology, vol. 229, pp. 183-192 (1997), Article No. VY968431.
[cited by applicant]
Santiago-Ortiz, et al., “AAV ancestral reconstruction library enables selection of broadly infectious viral variants,” Gene Therapy (2015), 22, 934-946, doi:10.1038/gt.2015.74, Epub Jul. 17, 2015.
[cited by applicant]
Shade, R.O., et al. “Nucleotide Sequence and Genome Organization of Human Parvovirus B19 Isolated from the Serum of a Child during Aplastic Crisis,” Journal of Virology, Jun. 1986, vol. 58, No. 3, pp. 921-936.
[cited by applicant]
Shen, X. et al. “Characterization of the Relationship of AAV Capsid Domain Swapping to Liver Transduction Efficiency,” Molecular Therapy, vol. 15, No. 11, pp. 1955-1962 (Nov. 2007), doi:10.1038/sj.mt.6300293.
[cited by applicant]
Srivistava, A., et al., “Nucleotide Sequence and Organization of the Adeno-Associated Virus 2 Genome,” Journal of Virology, vol. 45, No. 2, pp. 555-564 (Feb. 1983).
[cited by applicant]
Van Vliet, K. et al., “Proteolytic Mapping of the Adeno-associated Virus Capsid,” Molecular Therapy, vol. 14, No. 6, pp. 809-821 (Dec. 2006), doi:10.1016/j.ymthe.2006.08.1222.
[cited by applicant]
Wu, Z. et al., “Effect of Genome Size on AAV Vector Packaging,” Molecular Therapy, vol. 18, No. 1, pp. 80-86 (Jan. 2010).
[cited by applicant]
Xiao, W. et al., “Gene Therapy Vectors Based on Adeno-Associated Virus Type 1,” Journal of Virology, vol. 73, No. 5, pp. 3994-4003 (May 1999).
[cited by applicant]
Xie, Q. et al., “The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy,” Proceeding of the National Academy of Sciences, vol. 99, No. 16, pp. 10405-10410 (Aug. 2002), doi:10.1073/pnas.1…
[cited by applicant]
Addis et al. Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. J Mol Cell Cardiol 60:97-106 (2013).
[cited by applicant]
Akdis et al. Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls. Heart Rhy…
[cited by applicant]
Ali et al. Adena-associated virus gene transfer to mouse retina. Hum Gene Ther 9:81- 86 (1998).
[cited by applicant]
Ali et al. Gene transfer into the mouse retina mediated by an adeno-associated viral vector. Hum Mol Genet 5:591-594 (1996).
[cited by applicant]
Asimaki et al. A New Diagnostic Test for Arrhythmogenic Right Ventricular Cardiomyopathy. N Engl J Med 360(11):1075-84 (2009).
[cited by applicant]
Asokan et al. An emerging adeno-associated viral vector pipeline for cardiac gene therapy. Hum Gene Ther. 24:906-13 (2013).
[cited by applicant]
Balaji et al. Pseudotyped adeno-associated viral vectors for gene transfer in dermal fibroblasts: implications for wound-healing applications. J Surg Res. 184:691-98 (2013).
[cited by applicant]
Bellaiche et al. I-Scel Endonuclease, a New Tool for Studying DNA Double-Strand Break Repair Mechanisms in Drosophila. Genetics 152:1037-1044 (1999).
[cited by applicant]
Bennett et al. Real-time, noninvasive in vivo assessment of adeno-associated virus- mediated retinal transduction. Invest Ophthalmol Vis Sci. 38(13):2857-2863 (1997).
[cited by applicant]
Bitter et al. Expression and secretion vectors for yeast. Methods Enzymol 153:516-544 (1987).
[cited by applicant]
Blomer et al. Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector. J Virol. 71 (9) :6641-6649, 1997.
[cited by applicant]
Borras et al. Adenoviral reporter gene transfer to the human trabecular meshwork does not alter aqueous humor outflow. Relevance for potential gene therapy of glaucoma. Gene Ther 6(4):515-524 (1999).
[cited by applicant]
Bradford., et al., Plakophilin2 gene therapy prevents and rescues arrhythmogenic right ventricular cardiomyopathy in a mouse model harboring patient genetics, Nature Cardiovascular Research, 2023, pp. 1246-1261.
[cited by applicant]
Brodehl et al. Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies. Int. J. Mol. Sci. 20:4381 (2019), 56 pages.
[cited by applicant]
Brodehl et al. Molecular insights into cardiomyopathies associated with desmin (DES) mutations. Biophysical Reviews 10:983-1006 (2018).
[cited by applicant]
Burke et al. Arrhythmogenic right ventricular cardiomyopathy and fatty replacement of the right ventricular myocardium: are they different diseases? Circulation 97(16):1571-1580 (1998).
[cited by applicant]
Cerrone et al. Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm. Nat Commun 8(1):106 (2017), 16 pages.
[cited by applicant]
Chamberlain et al. Cardiac Gene Therapy with Adeno-Associated Virus-Based Vectors. Curr Opin Cardiol 32(3):275-282 (2017).
[cited by applicant]
Christoforou et al. Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming. PLoS One 8:e63577 (2013), 19 pages.
[cited by applicant]
Chu, D et al., “Gene delivery to the mammalian heart using AAV vectors,” Methods Mol Biol, 246:213-224 (2004).
[cited by applicant]
Chu et al. SV40 DNA transfection of cells in suspension: analysis of efficiency of transcription and translation of T-antigen. Gene 13:197-202 (1981).
[cited by applicant]
Cotten et al. High-efficiency receptor-mediated delivery of small and large (48 kilobase gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles. PNAS USA 89(13…
[cited by applicant]
Cruz et al. Exercise triggers ARVC phenotype in mice expressing a disease-causing mutated version of human plakophilin-2. J Am Coll Cardiol 65(14):1438-1450 (2015).
[cited by applicant]
Curiel et al. High-efficiency gene transfer employing adenovirus-polylysine-DNA complexes. Nat Immun 13(2-3):141-64 (1994).
[cited by applicant]
Daya et al., “Gene therapy using adeno-associated virus vectors.” Clin Microbial Rev. Oct. 2008; 21(4): 583-593.
[cited by applicant]
De et al. High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol. The…
[cited by applicant]
Dull et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 71 (11):8463-8471 (1998).
[cited by applicant]
Dziennis et al. The CD11 b promoter directs high-level expression of reporter genes in macrophages in transgenic mice. Blood 85(2):319-329 (1995).
[cited by applicant]
Faust et al. Insertion of enhanced green fluorescent protein into the lysozyme gene creates mice with green fluorescent granulocytes and macrophages. Blood 96(2):719-726 (2000).
[cited by applicant]
Flannery et al. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. PNAS USA 94(13):6916-6921 (1997).
[cited by applicant]
Flotte et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. PNAS USA 90(22):10613-10617 (1993).
[cited by applicant]
Franz et al. Analysis of tissue-specific gene delivery by recombinant adenoviruses containing cardiac-specific promoters. Cardiovasc. Res. 35:560-566 (1997).
[cited by applicant]
Fu et al. Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Reports 1 :235-247 (2013).
[cited by applicant]
Gao et al.: Clades of Adeno-associated viruses are widely disseminated in human tissues. J Virol. 78(12): 6381-6388 (2004).
[cited by applicant]
Gerull et al. Genetic Animal Models for Arrhythmogenic Cardiomyopathy. Front Physiol 11 :624 (2020), 20 pages.
[cited by applicant]
Graham et al. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456-467 (1973).
[cited by applicant]
Grainger et al. 870. Transfection of Mammalian Cells Using Linear Polyethylenimine Is a Simple and Effective Means of Producing Recombinant AAV. Mol Ther 11 :S337 (2005), 2 pages.
[cited by applicant]
Green et al. Desmosomes: Essential contributors to an integrated intercellular junction network. F1000Res F1000 Faculty Rev-2150 (2019), 16 pages.
[cited by applicant]
He et al. Development of a synthetic promoter for macrophage gene therapy. Hum Gene Ther 17:949-959 (2006).
[cited by applicant]
Heath et al. The structure of I-Crel, a Group I intron-encoded homing endonuclease. Nat Struct Biol 4:468 (1997), 9 pages.
[cited by applicant]
Hu et al., MicroRNA-302 increases reprogramming efficiency via repression of NR2F2. Stem Cells 31 (2):259-68 (2013).
[cited by applicant]
Hunter et al. Targeting gene expression to specific cardiovascular cell types in transgenic mice. Hypertension 22:608-617 (1993).
[cited by applicant]
Ieda et al.: Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 142(3):375-386 (2010).
[cited by applicant]
Ishikawa., et al., Human Cardiac Gene Therapy, Circulation Research, 2018, pp. 601-613.
[cited by applicant]
Jayawardena et al. MicroRNA-Mediated In Vitro and In Vivo Direct Reprogramming of Cardiac Fibroblasts to Cardiomyocytes, Circ. Res. 110:1465-1473 (2012).
[cited by applicant]
Jomary et al. Rescue of photoreceptor function by AAV-mediated gene transfer in a mouse model of inherited retinal degeneration. Gene Ther. 4(7):683-690 (1997).
[cited by applicant]
Kanegae et al. Efficient gene activation in mammalian cells by using recombinant adenovirus expressing site-specific Cre recombinase. Nucleic Acids Res 23:3816-3821 (1995).
[cited by applicant]
Karakikes et al. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Insights into Molecular, Cellular, and Functional Phenotypes, Circ Res. 117(1):80-88 (2015).
[cited by applicant]
Katz, M.G. et al., “Cardiac gene therapy: optimization of gene delivery techniques in vivo,” Human Gene Therapy, 21:371-380 (2010).
[cited by applicant]
Kelleher et al. Long-term episomal gene delivery in human lymphoid cells using human and avian adenoviral-assisted transfection. Biotechniques 17(6):1110-7 (1994).
[cited by applicant]
Kim et al. Direct reprogramming of mouse fibroblasts to neural progenitors. PNAS USA 108(19):7838-7843 (2011).
[cited by applicant]
Kitamura et al. Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics. Exp Hematol 31:1007-1014 (2003).
[cited by applicant]
Korpela, et al, Gene therapy for ischaemic heart disease and heart failure, Intern Med 2021; 290: 567-582.
[cited by applicant]
Kotterman et al. Engineering adeno-associated viruses for clinical gene therapy. Nature Reviews Genetics 15:445-451 (2014).
[cited by applicant]
Kraus et al. S100A1 in cardiovascular health and disease: closing the gap between basic science and clinical therapy. Mol Cell Cardiol 47:445-455 (2009).
[cited by applicant]
Lee et al. Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine. Genes Dis 4(2):43-63 (2017).
[cited by applicant]
Li et al. In vivo transfer of a reporter gene to the retina mediated by an adenoviral vector. Invest Opthalmol Vis Sci 35:2543-2549 (1994).
[cited by applicant]
Li et al. Phenotype correction in retinal pigment epithelium in murine mucopolysaccharidosis VII by adenovirus-mediated gene transfer. PNAS USA 92:7700-7704 (1995).
[cited by applicant]
Linn et al. Conservation of an AE3 CI-/HCO3-exchanger cardiac-specific exon and promoter region and AE3 mRNA expression patterns in murine and human hearts. Circ. Res. 76:584-591 (1995).
[cited by applicant]
Macejak et al., Internal initiation of translation mediated by the 5′ leader of a cellular mRNA. Nature 353:90-94 (1991).
[cited by applicant]
Mann et al. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell 33:153-159 (1983).
[cited by applicant]
Matkar, P. N. et al., “Cardiac gene therapy: are we there yet?” Gene Therapy, 23:635-648 (2016).
[cited by applicant]
Mauro. Codon Optimization in the Production of Recombinant Biotherapeutics: Potential Risks and Considerations. BioDrugs 32:69-81 (2018).
[cited by applicant]
Mendelson et al. Expression and rescue of a nonselected marker from an integrated AAV vector. Virology 166(1):154-165 (1988).
[cited by applicant]
Miller et al. Radiation resistance in a doxorubicin-resistant human fibrosarcoma cell line. Am. J. Clin. Oncol. 15(3):216-221 (1992).
[cited by applicant]
Miyoshi et al. Development of a self-inactivating lentivirus vector. J. Virol 72(10):8150-8157 (1998).
[cited by applicant]
Miyoshi et al. Stable and efficient gene transfer into the retina using an HIV-based lentiviral vector. PNAS USA 94(19):10319-10323 (1997).
[cited by applicant]
Moncayo-Arlandi et al. Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada syndrome. Nat Rev Cardiol 14(12):744-756 (2017).
[cited by applicant]
Morgenstern et al. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. Nucleic Acids Res. 18(12):3587-3596 (1990).
[cited by applicant]
Morita et al. Plat-E: an efficient and stable system for transient packaging of retroviruses. Gene Therapy 7(12):1063-1066 (2000).
[cited by applicant]
Mura et al. Identification of a PKP2 gene deletion in a family with arrhythmogenic right ventricular cardiomyopathy. Eur J Hum Genet 21 (11):1226-1231 (2003).
[cited by applicant]
Naldini et al. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263-7 (1996).
[cited by applicant]
Naldini et al. Lentiviruses as gene transfer agents for delivery to non-dividing cells. Curr Opin Biotechnol. 9(5):457-463 (1998).
[cited by applicant]
Nam et al. Reprogramming of human fibroblasts toward a cardiac fate. PNAS USA 110:5588-5593 (2003).
[cited by applicant]
Narayanan et al. Preclinical Efficacy of AAVrh.74-PKP2a (RP-A601): Gene Therapy for PKP2-Associated Arrhythmogenic Cardiomyopathy (PKP2-ACM), Molecular Therapy, 26th Annual Meeting of the American Society of Gene and Ce…
[cited by applicant]
Nicolas et al. Chapter 25: Retroviral Vectors. In Vectors: A survey of molecular cloning vectors and their uses Rodriguez and Denhardt eds. Stoneham: Butterworth (pp. 493-513) (1988).
[cited by applicant]
Onishi et al. Applications of retrovirus-mediated expression cloning. Exp Hematol 24:324-329 (1996).
[cited by applicant]
Pacak et al. Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice. Genet Vaccines Ther. 6:13 (2008), 5 pages.
[cited by applicant]
Park, Frank, “The heart is where AAV9 lies,” Physiol Genomics 54: 316-318, 2022.
[cited by applicant]
Parmacek et al. A novel myogenic regulatory circuit controls slow/cardiac troponin C gene transcription in skeletal muscle. Mol Cell Biol 14:1870-1885 (1994).
[cited by applicant]
Paskind et al. Dependence of Moloney murine leukemia virus production on cell growth. Virology 67:242-248 (1975).
[cited by applicant]
Pelletier et al., Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334:320-325 (1988).
[cited by applicant]
Piras et al. Systemic injection of AAV9 carrying a periostin promoter targets gene expression to a myofibroblast-like lineage in mouse hearts after reperfused myocardial infarction. Gene Therapy 23:469-478 (2016).
[cited by applicant]
Powell, S. K., et al., “Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy”, Discovery Medicine (2015); 19(102): 49-57.
[cited by applicant]
Pozsgai et al. Systemic AA V-Mediated β-Sarcoglycan Delivery Targeting Cardiac and Skeletal Muscle Ameliorates Histological and Functional Deficits in LGMD2E Mice. Mol Ther. 25:855-69 (2017).
[cited by applicant]
Presnyak et al. Codon optimality is a major determinant of mRNA stability. Cell 160(6):1111-1124 (2015).
[cited by applicant]
Ritterhoff et al., Targeting S100A1 in heart failure. Gene Ther. 19(6):613-621 (2012).
[cited by applicant]
Riviere et al. Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells. PNAS USA 92(15):6733-6737 (1995).
[cited by applicant]
Robbins et al. In vivo definition of a cardiac specific promoter and its potential utility in remodeling the heart. Ann. N.Y. Acad. Sci.752:492-505 (1995).
[cited by applicant]
Rolling et al. Evaluation of adeno-associated virus-mediated gene transfer into the rat retina by clinical fluorescence photography. Hum Gene Ther 10:641-648 (1999).
[cited by applicant]
Sakamoto et al. A vitrectomy improves the transfection efficiency of adenoviral vector-mediated gene transfer to Muller cells. Gene Ther. 5(8):1088-1097 (1998).
[cited by applicant]
Samulski et al. Helper-free stocks of recombinant adeno-associated viruses: normal integration does not require viral gene expression. J Virol. 63(9):3822-3828 (1989).
[cited by applicant]
Sartorelli et al. Myocardial activation of the human cardiac α-actin promoter by helix-loop-helix proteins. PNAS USA 89:4047-4051 (1992).
[cited by applicant]
Shanks et al., “Are animal models predictive for humans?”, Philosophy, Ethics, and Humanities in Medicine, 2009, pp. 1-20.
[cited by applicant]
Shpaer. GeneAssist. Smith-Waterman and other database similarity searches and identification of motifs. Methods Mol Biol 70:173-187 (1997).
[cited by applicant]
Singh., et al., A Review on Arrhythmogenic Right Ventricular Cardiomyopathy—Pathogenesis, Diagnosis and Treatment Modalities, International Journal of Research Publication and Reviews, vol. 3, No. 12, pp. 2448-2455, Dec…
[cited by applicant]
Takahashi et al. Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol 73:7812-7816 (1999).
[cited by applicant]
Temin. Chapter 6: Retrovirus Vectors for Gene Transfer: Efficient Integration into and Expression of Exogenous DNA in Vertebrate Cell Genomes. Gene Transfer Kucherlapati (ed.) New York: Plenum Press (pp. 149-188) (1986).
[cited by applicant]
Wada et al. Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. PNAS USA 110:12667-12672 (2013).
[cited by applicant]
Wang et al. Diagnostic and therapeutic strategies for arrhythmogenic right ventricular dysplasia/cardiomyopathy patient. Europace 21 (1):9-21 (2018).
[cited by applicant]
Wu et al. Cardiac AAV:PKP2 Gene Therapy Reduces Ventricular Arrhythmias, Reverses Adverse Right Ventricular Remodeling, Improves Heart Function, and Extends Survival in a Pkp2-deficient Mouse Model of Arrhythmogenic Rig…
[cited by applicant]
Yee et al. A General Method for the Generation of High-Titer, Pantropic Retroviral Vectors: Highly Efficient Infection of Primary Hepatocytes. PNAS USA 91 :9564-9568 (1994), 5 pages.
[cited by applicant]
Zolotukhin et al. Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther 6:973-985 (1999).
[cited by applicant]
Zufferey et al. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15(9):871-875 (1997).
[cited by applicant]
Bogner, et al., “Capsid Mutated Adeno-Associated Virus Delivered to the Anterior Chamber Results in Efficient Transduction of Trabecular Meshwork in Mouse and Rat,” PLoS One. Jun. 8, 2015; 10(6):e0128759, 16 pages.
[cited by applicant]
Hirai, et al., “Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain,” Cardiovasc Res. Oct. 1, 2013; 100(1):105-13. Epub Jun. 20, 2013.
[cited by applicant]
Rasmussen, et al., “Truncating plakophilin-2 mutations in arrhythmogenic cardiomyopathy are associated with protein haploinsufficiency in both myocardium and epidermis,” Circ Cardiovasc Genet. Jun. 2014; 7(3):230-40. Ep…
[cited by applicant]
Van Opbergen, et al., “AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans,” Circ Genom…
[cited by applicant]
Van Opbergen, et al., “Plakophilin-2 Haploinsufficiency Causes Calcium Handling Deficits and Modulates the Cardiac Response Towards Stress,” Int J Mol Sci. Aug. 21, 2019; 20(17):4076, pp. 1-21.
[cited by applicant]
Wu, et al., “Cardiac AAV9:PKP2 Gene Therapy Reduces Ventricular Arrhythmias, Reverses Adverse Remodeling, and Reduces Mortality in a Mouse Model of ARVC,” Research Square 2023, 42 pages retrieved online at: https://asse…
[cited by applicant]