Gene Editing for the Treatment of Hypercholesterolemia

go back to reference Kannel WB, Wilson PW. Efficacy of lipid profiles in prediction of coronary disease. Am Heart J. 1992;124:768–74. https://doi.org/10.1016/0002-8703(92)90288-7.CrossRefPubMed Kannel WB, Wilson PW. Efficacy of lipid profiles in prediction of coronary disease. Am Heart J. 1992;124:768–74. https://​doi.​org/​10.​1016/​0002-8703(92)90288-7.CrossRefPubMed

go back to reference Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease, and death. The Framingham study Arch Intern Med. 1981;141:1128–31.CrossRefPubMed Gordon T, Kannel WB, Castelli WP, Dawber TR. Lipoproteins, cardiovascular disease, and death. The Framingham study Arch Intern Med. 1981;141:1128–31.CrossRefPubMed

go back to reference Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Tsao CW Heart Disease and Stroke Statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143:e254–743. https://doi.org/10.1161/CIR.0000000000000950.CrossRefPubMed Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Tsao CW Heart Disease and Stroke Statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143:e254–743. https://​doi.​org/​10.​1161/​CIR.​0000000000000950​.CrossRefPubMed

go back to reference Annual Report 2021 Dutch Heart Foundation / Jaarverslag 2021 Hartstichting (https://magazines.hartstichting.nl/jaarverslag-2021/downloaden-jaarverslag). Annual Report 2021 Dutch Heart Foundation / Jaarverslag 2021 Hartstichting (https://​magazines.​hartstichting.​nl/​jaarverslag-2021/​downloaden-jaarverslag).

go back to reference Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011:CD004816. https://doi.org/10.1002/14651858.CD004816.pub4. Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011:CD004816. https://​doi.​org/​10.​1002/​14651858.​CD004816.​pub4.

go back to reference Zhu Y, Chiang CW, Wang L, Brock G, Milks MW, Cao W, Zhang P, Zeng D, Donneyong M, Li L. A multistate transition model for statin-induced myopathy and statin discontinuation. CPT Pharmacometrics Syst Pharmacol. 2021;10:1236–44. https://doi.org/10.1002/psp4.12691.CrossRefPubMedPubMedCentral Zhu Y, Chiang CW, Wang L, Brock G, Milks MW, Cao W, Zhang P, Zeng D, Donneyong M, Li L. A multistate transition model for statin-induced myopathy and statin discontinuation. CPT Pharmacometrics Syst Pharmacol. 2021;10:1236–44. https://​doi.​org/​10.​1002/​psp4.​12691.CrossRefPubMedPubMedCentral

go back to reference Ginn SL, Christina S, Alexander IE. Genome editing in the human liver: progress and translational considerations. Prog Mol Biol Transl Sci. 2021;182:257–88. https://doi.org/10.1016/bs.pmbts.2021.01.030.CrossRefPubMed Ginn SL, Christina S, Alexander IE. Genome editing in the human liver: progress and translational considerations. Prog Mol Biol Transl Sci. 2021;182:257–88. https://​doi.​org/​10.​1016/​bs.​pmbts.​2021.​01.​030.CrossRefPubMed

go back to reference Raper SE, Yudkoff M, Chirmule N, Gao GP, Nunes F, Haskal ZJ, Furth EE, Propert KJ, Robinson MB, Magosin S, Simoes H, Speicher L, Hughes J, Tazelaar J, Wivel NA, Wilson JM, Batshaw ML. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther. 2002;13:163–75. https://doi.org/10.1089/10430340152712719.CrossRefPubMed Raper SE, Yudkoff M, Chirmule N, Gao GP, Nunes F, Haskal ZJ, Furth EE, Propert KJ, Robinson MB, Magosin S, Simoes H, Speicher L, Hughes J, Tazelaar J, Wivel NA, Wilson JM, Batshaw ML. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther. 2002;13:163–75. https://​doi.​org/​10.​1089/​1043034015271271​9.CrossRefPubMed

go back to reference Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003;80:148–58. https://doi.org/10.1016/j.ymgme.2003.08.016.CrossRefPubMed Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao GP, Wilson JM, Batshaw ML. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003;80:148–58. https://​doi.​org/​10.​1016/​j.​ymgme.​2003.​08.​016.CrossRefPubMed

go back to reference Pipe SW, Leebeek FWG, Recht M, Key NS, Castaman G, Miesbach W, Lattimore S, Peerlinck K, Van der Valk P, Coppens M, Kampmann P, Meijer K, O’Connell N, Pasi KJ, Hart DP, Kazmi R, Astermark J, Hermans CRJR, Klamroth R, Lemons R, Visweshwar N, von Drygalski A, Young G, Crary SE, Escobar M, Gomez E, Kruse-Jarres R, Quon DV, Symington E, Wang M, Wheeler AP, Gut R, Liu YP, Dolmetsch RE, Cooper DL, Li Y, Goldstein B, Monahan PE. Gene therapy with etranacogene dezaparvovec for hemophilia b. N Engl J Med. 2023;388:706–18. https://doi.org/10.1056/NEJMoa2211644.CrossRefPubMed Pipe SW, Leebeek FWG, Recht M, Key NS, Castaman G, Miesbach W, Lattimore S, Peerlinck K, Van der Valk P, Coppens M, Kampmann P, Meijer K, O’Connell N, Pasi KJ, Hart DP, Kazmi R, Astermark J, Hermans CRJR, Klamroth R, Lemons R, Visweshwar N, von Drygalski A, Young G, Crary SE, Escobar M, Gomez E, Kruse-Jarres R, Quon DV, Symington E, Wang M, Wheeler AP, Gut R, Liu YP, Dolmetsch RE, Cooper DL, Li Y, Goldstein B, Monahan PE. Gene therapy with etranacogene dezaparvovec for hemophilia b. N Engl J Med. 2023;388:706–18. https://​doi.​org/​10.​1056/​NEJMoa2211644.CrossRefPubMed

go back to reference Rensen PC, Sliedregt LA, Ferns M, Kieviet E, van Rossenberg SM, van Leeuwen SH, van Berkel TJ, Biessen EA. Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and in vivo. J Biol Chem. 2001;276:37577–84. https://doi.org/10.1074/jbc.M101786200.CrossRefPubMed Rensen PC, Sliedregt LA, Ferns M, Kieviet E, van Rossenberg SM, van Leeuwen SH, van Berkel TJ, Biessen EA. Determination of the upper size limit for uptake and processing of ligands by the asialoglycoprotein receptor on hepatocytes in vitro and in vivo. J Biol Chem. 2001;276:37577–84. https://​doi.​org/​10.​1074/​jbc.​M101786200.CrossRefPubMed

go back to reference Biessen EA, Sliedregt-Bol K, T Hoen PA, Prince P, Van der Bilt E, Valentijn AR, Meeuwenoord NJ, Princen H, Bijsterbosch MK, Van der Marel GA, Van Boom JH, Van Berkel TJ. Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepatocytes. Bioconjug Chem. 2002:13:295–302 https://doi.org/10.1021/bc015550g. Biessen EA, Sliedregt-Bol K, T Hoen PA, Prince P, Van der Bilt E, Valentijn AR, Meeuwenoord NJ, Princen H, Bijsterbosch MK, Van der Marel GA, Van Boom JH, Van Berkel TJ. Design of a targeted peptide nucleic acid prodrug to inhibit hepatic human microsomal triglyceride transfer protein expression in hepatocytes. Bioconjug Chem. 2002:13:295–302 https://​doi.​org/​10.​1021/​bc015550g.

go back to reference Nair JK, Willoughby JL, Chan A, Charisse K, Alam MR, Wang Q, Hoekstra M, Kandasamy P, Kel’in AV, Milstein S, Taneja N, O’Shea J, Shaikh S, Zhang L, van der Sluis RJ, Jung ME, Akinc A, Hutabarat R, Kuchimanchi S, Fitzgerald K, Zimmermann T, van Berkel TJ, Maier MA, Rajeev KG, Manoharan M. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc. 2014;136:16958–61. https://doi.org/10.1021/ja505986a.CrossRefPubMed Nair JK, Willoughby JL, Chan A, Charisse K, Alam MR, Wang Q, Hoekstra M, Kandasamy P, Kel’in AV, Milstein S, Taneja N, O’Shea J, Shaikh S, Zhang L, van der Sluis RJ, Jung ME, Akinc A, Hutabarat R, Kuchimanchi S, Fitzgerald K, Zimmermann T, van Berkel TJ, Maier MA, Rajeev KG, Manoharan M. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J Am Chem Soc. 2014;136:16958–61. https://​doi.​org/​10.​1021/​ja505986a.CrossRefPubMed

go back to reference Kasiewicz LN, Biswas S, Beach A, Ren H, Dutta C, Mazzola AM, Rohde E, Chadwick A, Cheng C, Garcia SP, Iyer S, Matsumoto Y, Khera AV, Musunuru K, Kathiresan S, Malyala P, Rajeev KG, Bellinger AM. GalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy. Nat Commun. 2023;14:2776. https://doi.org/10.1038/s41467-023-37465-1.CrossRefPubMedPubMedCentral Kasiewicz LN, Biswas S, Beach A, Ren H, Dutta C, Mazzola AM, Rohde E, Chadwick A, Cheng C, Garcia SP, Iyer S, Matsumoto Y, Khera AV, Musunuru K, Kathiresan S, Malyala P, Rajeev KG, Bellinger AM. GalNAc-Lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy. Nat Commun. 2023;14:2776. https://​doi.​org/​10.​1038/​s41467-023-37465-1.CrossRefPubMedPubMedCentral

go back to reference Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, van Leeuwen EM, Natarajan P, Emdin CA, Bick AG, Morrison AC, Brody JA, Gupta N, Nomura A, Kessler T, Duga S, Bis JC, van Duijn CM, Cupples LA, Psaty B, Rader DJ, Danesh J, Schunkert H, McPherson R, Farrall M, Watkins H, Lander E, Wilson JG, Correa A, Boerwinkle E, Merlini PA, Ardissino D, Saleheen D, Gabriel S, Kathiresan S. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578–89. https://doi.org/10.1016/j.jacc.2016.03.520.CrossRefPubMedPubMedCentral Khera AV, Won HH, Peloso GM, Lawson KS, Bartz TM, Deng X, van Leeuwen EM, Natarajan P, Emdin CA, Bick AG, Morrison AC, Brody JA, Gupta N, Nomura A, Kessler T, Duga S, Bis JC, van Duijn CM, Cupples LA, Psaty B, Rader DJ, Danesh J, Schunkert H, McPherson R, Farrall M, Watkins H, Lander E, Wilson JG, Correa A, Boerwinkle E, Merlini PA, Ardissino D, Saleheen D, Gabriel S, Kathiresan S. Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578–89. https://​doi.​org/​10.​1016/​j.​jacc.​2016.​03.​520.CrossRefPubMedPubMedCentral

go back to reference Zhao H, Li Y, He L, Pu W, Yu W, Li Y, Wu YT, Xu C, Wei Y, Ding Q, Song BL, Huang H, Zhou B. In vivo AAV-CRISPR/Cas9-mediated gene editing ameliorates atherosclerosis in familial hypercholesterolemia. Circulation. 2020;141:67–79. https://doi.org/10.1161/CIRCULATIONAHA.119.042476.CrossRefPubMed Zhao H, Li Y, He L, Pu W, Yu W, Li Y, Wu YT, Xu C, Wei Y, Ding Q, Song BL, Huang H, Zhou B. In vivo AAV-CRISPR/Cas9-mediated gene editing ameliorates atherosclerosis in familial hypercholesterolemia. Circulation. 2020;141:67–79. https://​doi.​org/​10.​1161/​CIRCULATIONAHA.​119.​042476.CrossRefPubMed

go back to reference Jarrett KE, Lee CM, Yeh YH, Hsu RH, Gupta R, Zhang M, Rodriguez PJ, Lee CS, Gillard BK, Bissig KD, Pownall HJ, Martin JF, Bao G, Lagor WR. Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease. Sci Rep. 2017;7:44624. https://doi.org/10.1038/srep44624.CrossRefPubMedPubMedCentral Jarrett KE, Lee CM, Yeh YH, Hsu RH, Gupta R, Zhang M, Rodriguez PJ, Lee CS, Gillard BK, Bissig KD, Pownall HJ, Martin JF, Bao G, Lagor WR. Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease. Sci Rep. 2017;7:44624. https://​doi.​org/​10.​1038/​srep44624.CrossRefPubMedPubMedCentral

go back to reference Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37:161–5. https://doi.org/10.1038/ng1509.CrossRefPubMed Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet. 2005;37:161–5. https://​doi.​org/​10.​1038/​ng1509.CrossRefPubMed

go back to reference Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264–72. https://doi.org/10.1056/NEJMoa054013.CrossRefPubMed Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354:1264–72. https://​doi.​org/​10.​1056/​NEJMoa054013.CrossRefPubMed

go back to reference Dugré N, Lindblad AJ, Perry D, Allan GM, Braschi É, Falk J, Froentjes L, Garrison SR, Kirkwood JEM, Korownyk CS, McCormack JP, Moe SS, Paige A, Potter J, Thomas BS, Ton J, Young J, Weresch J, Kolber MR. Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews. Can Fam Physician. 2023;69:701–11. https://doi.org/10.46747/cfp.6910701.CrossRefPubMedPubMedCentral Dugré N, Lindblad AJ, Perry D, Allan GM, Braschi É, Falk J, Froentjes L, Garrison SR, Kirkwood JEM, Korownyk CS, McCormack JP, Moe SS, Paige A, Potter J, Thomas BS, Ton J, Young J, Weresch J, Kolber MR. Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews. Can Fam Physician. 2023;69:701–11. https://​doi.​org/​10.​46747/​cfp.​6910701.CrossRefPubMedPubMedCentral

go back to reference Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Cowan CA, Rader DJ, Musunuru K. Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res. 2014;115:488–92. https://doi.org/10.1161/CIRCRESAHA.115.304351.CrossRefPubMedPubMedCentral Ding Q, Strong A, Patel KM, Ng SL, Gosis BS, Regan SN, Cowan CA, Rader DJ, Musunuru K. Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res. 2014;115:488–92. https://​doi.​org/​10.​1161/​CIRCRESAHA.​115.​304351.CrossRefPubMedPubMedCentral

go back to reference Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520:186–91. https://doi.org/10.1038/nature14299.CrossRefPubMedPubMedCentral Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520:186–91. https://​doi.​org/​10.​1038/​nature14299.CrossRefPubMedPubMedCentral

go back to reference Chadwick AC, Wang X, Musunuru K. In vivo base editing of PCSK9 (proprotein convertase Subtilisin/Kexin Type 9) as a therapeutic alternative to genome editing. Arterioscler Thromb Vasc Biol. 2017;37:1741–7. https://doi.org/10.1161/ATVBAHA.117.309881.CrossRefPubMedPubMedCentral Chadwick AC, Wang X, Musunuru K. In vivo base editing of PCSK9 (proprotein convertase Subtilisin/Kexin Type 9) as a therapeutic alternative to genome editing. Arterioscler Thromb Vasc Biol. 2017;37:1741–7. https://​doi.​org/​10.​1161/​ATVBAHA.​117.​309881.CrossRefPubMedPubMedCentral

go back to reference Jiang C, Mei M, Li B, Zhu X, Zu W, Tian Y, Wang Q, Guo Y, Dong Y, Tan X. A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell Res. 2017;27:440–3. https://doi.org/10.1038/cr.2017.16.CrossRefPubMedPubMedCentral Jiang C, Mei M, Li B, Zhu X, Zu W, Tian Y, Wang Q, Guo Y, Dong Y, Tan X. A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell Res. 2017;27:440–3. https://​doi.​org/​10.​1038/​cr.​2017.​16.CrossRefPubMedPubMedCentral

go back to reference Zhang L, Wang L, Xie Y, Wang P, Deng S, Qin A, Zhang J, Yu X, Zheng W, Jiang X. Triple-targeting delivery of CRISPR/Cas9 to reduce the risk of cardiovascular diseases. Angew Chem Int Ed Engl. 2019;58:12404–8. https://doi.org/10.1002/anie.201903618.CrossRefPubMed Zhang L, Wang L, Xie Y, Wang P, Deng S, Qin A, Zhang J, Yu X, Zheng W, Jiang X. Triple-targeting delivery of CRISPR/Cas9 to reduce the risk of cardiovascular diseases. Angew Chem Int Ed Engl. 2019;58:12404–8. https://​doi.​org/​10.​1002/​anie.​201903618.CrossRefPubMed

go back to reference Wang L, Smith J, Breton C, Clark P, Zhang J, Ying L, Che Y, Lape J, Bell P, Calcedo R, Buza EL, Saveliev A, Bartsevich VV, He Z, White J, Li M, Jantz D, Wilson JM. Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol. Nat Biotechnol. 2018;36:717–25. https://doi.org/10.1038/nbt.4182.CrossRefPubMed Wang L, Smith J, Breton C, Clark P, Zhang J, Ying L, Che Y, Lape J, Bell P, Calcedo R, Buza EL, Saveliev A, Bartsevich VV, He Z, White J, Li M, Jantz D, Wilson JM. Meganuclease targeting of PCSK9 in macaque liver leads to stable reduction in serum cholesterol. Nat Biotechnol. 2018;36:717–25. https://​doi.​org/​10.​1038/​nbt.​4182.CrossRefPubMed

go back to reference Breton C, Furmanak T, Avitto AN, Smith MK, Latshaw C, Yan H, Greig JA, Wilson JM. Increasing the specificity of AAV-based gene editing through self-targeting and short-promoter strategies. Mol Ther. 2021;29:1047–56. https://doi.org/10.1016/j.ymthe.2020.12.028.CrossRefPubMed Breton C, Furmanak T, Avitto AN, Smith MK, Latshaw C, Yan H, Greig JA, Wilson JM. Increasing the specificity of AAV-based gene editing through self-targeting and short-promoter strategies. Mol Ther. 2021;29:1047–56. https://​doi.​org/​10.​1016/​j.​ymthe.​2020.​12.​028.CrossRefPubMed

go back to reference Rothgangl T, Dennis MK, Lin PJC, Oka R, Witzigmann D, Villiger L, Qi W, Hruzova M, Kissling L, Lenggenhager D, Borrelli C, Egli S, Frey N, Bakker N, Walker JA 2nd, Kadina AP, Victorov DV, Pacesa M, Kreutzer S, Kontarakis Z, Moor A, Jinek M, Weissman D, Stoffel M, van Boxtel R, Holden K, Pardi N, Thöny B, Häberle J, Tam YK, Semple SC, Schwank G. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat Biotechnol. 2021;39:949–57. https://doi.org/10.1038/s41587-021-00933-4.CrossRefPubMedPubMedCentral Rothgangl T, Dennis MK, Lin PJC, Oka R, Witzigmann D, Villiger L, Qi W, Hruzova M, Kissling L, Lenggenhager D, Borrelli C, Egli S, Frey N, Bakker N, Walker JA 2nd, Kadina AP, Victorov DV, Pacesa M, Kreutzer S, Kontarakis Z, Moor A, Jinek M, Weissman D, Stoffel M, van Boxtel R, Holden K, Pardi N, Thöny B, Häberle J, Tam YK, Semple SC, Schwank G. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat Biotechnol. 2021;39:949–57. https://​doi.​org/​10.​1038/​s41587-021-00933-4.CrossRefPubMedPubMedCentral

go back to reference •• Musunuru K, Chadwick AC, Mizoguchi T, Garcia SP, DeNizio JE, Reiss CW, Wang K, Iyer S, Dutta C, Clendaniel V, Amaonye M, Beach A, Berth K, Biswas S, Braun MC, Chen HM, Colace TV, Ganey JD, Gangopadhyay SA, Garrity R, Kasiewicz LN, Lavoie J, Madsen JA, Matsumoto Y, Mazzola AM, Nasrullah YS, Nneji J, Ren H, Sanjeev A, Shay M, Stahley MR, Fan SHY, Tam YK, Gaudelli NM, Ciaramella G, Stolz LE, Malyala P, Cheng CJ, Rajeev KG, Rohde E, Bellinger AM, Kathiresan S. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature. 2021;593:429–34. https://doi.org/10.1038/s41586-021-03534-y. (Important preclinical proof from non-humane primates for lipid lowering potential of PCSK9 gene editing).CrossRefPubMed •• Musunuru K, Chadwick AC, Mizoguchi T, Garcia SP, DeNizio JE, Reiss CW, Wang K, Iyer S, Dutta C, Clendaniel V, Amaonye M, Beach A, Berth K, Biswas S, Braun MC, Chen HM, Colace TV, Ganey JD, Gangopadhyay SA, Garrity R, Kasiewicz LN, Lavoie J, Madsen JA, Matsumoto Y, Mazzola AM, Nasrullah YS, Nneji J, Ren H, Sanjeev A, Shay M, Stahley MR, Fan SHY, Tam YK, Gaudelli NM, Ciaramella G, Stolz LE, Malyala P, Cheng CJ, Rajeev KG, Rohde E, Bellinger AM, Kathiresan S. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature. 2021;593:429–34. https://​doi.​org/​10.​1038/​s41586-021-03534-y. (Important preclinical proof from non-humane primates for lipid lowering potential of PCSK9 gene editing).CrossRefPubMed

go back to reference Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O’Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PK, Lucas G, Luben R, Loos RJ, Lokki ML, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, König IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR, Janssens AC, Ingelsson E, Igl W, Kees Hovingh G, Hottenga JJ, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Döring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor HA Jr, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13. https://doi.org/10.1038/nature09270.CrossRefPubMedPubMedCentral Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, Pirruccello JP, Ripatti S, Chasman DI, Willer CJ, Johansen CT, Fouchier SW, Isaacs A, Peloso GM, Barbalic M, Ricketts SL, Bis JC, Aulchenko YS, Thorleifsson G, Feitosa MF, Chambers J, Orho-Melander M, Melander O, Johnson T, Li X, Guo X, Li M, Shin Cho Y, Jin Go M, Jin Kim Y, Lee JY, Park T, Kim K, Sim X, Twee-Hee Ong R, Croteau-Chonka DC, Lange LA, Smith JD, Song K, Hua Zhao J, Yuan X, Luan J, Lamina C, Ziegler A, Zhang W, Zee RY, Wright AF, Witteman JC, Wilson JF, Willemsen G, Wichmann HE, Whitfield JB, Waterworth DM, Wareham NJ, Waeber G, Vollenweider P, Voight BF, Vitart V, Uitterlinden AG, Uda M, Tuomilehto J, Thompson JR, Tanaka T, Surakka I, Stringham HM, Spector TD, Soranzo N, Smit JH, Sinisalo J, Silander K, Sijbrands EJ, Scuteri A, Scott J, Schlessinger D, Sanna S, Salomaa V, Saharinen J, Sabatti C, Ruokonen A, Rudan I, Rose LM, Roberts R, Rieder M, Psaty BM, Pramstaller PP, Pichler I, Perola M, Penninx BW, Pedersen NL, Pattaro C, Parker AN, Pare G, Oostra BA, O’Donnell CJ, Nieminen MS, Nickerson DA, Montgomery GW, Meitinger T, McPherson R, McCarthy MI, McArdle W, Masson D, Martin NG, Marroni F, Mangino M, Magnusson PK, Lucas G, Luben R, Loos RJ, Lokki ML, Lettre G, Langenberg C, Launer LJ, Lakatta EG, Laaksonen R, Kyvik KO, Kronenberg F, König IR, Khaw KT, Kaprio J, Kaplan LM, Johansson A, Jarvelin MR, Janssens AC, Ingelsson E, Igl W, Kees Hovingh G, Hottenga JJ, Hofman A, Hicks AA, Hengstenberg C, Heid IM, Hayward C, Havulinna AS, Hastie ND, Harris TB, Haritunians T, Hall AS, Gyllensten U, Guiducci C, Groop LC, Gonzalez E, Gieger C, Freimer NB, Ferrucci L, Erdmann J, Elliott P, Ejebe KG, Döring A, Dominiczak AF, Demissie S, Deloukas P, de Geus EJ, de Faire U, Crawford G, Collins FS, Chen YD, Caulfield MJ, Campbell H, Burtt NP, Bonnycastle LL, Boomsma DI, Boekholdt SM, Bergman RN, Barroso I, Bandinelli S, Ballantyne CM, Assimes TL, Quertermous T, Altshuler D, Seielstad M, Wong TY, Tai ES, Feranil AB, Kuzawa CW, Adair LS, Taylor HA Jr, Borecki IB, Gabriel SB, Wilson JG, Holm H, Thorsteinsdottir U, Gudnason V, Krauss RM, Mohlke KL, Ordovas JM, Munroe PB, Kooner JS, Tall AR, Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010;466:707–13. https://​doi.​org/​10.​1038/​nature09270.CrossRefPubMedPubMedCentral

go back to reference Qiu M, Glass Z, Chen J, Haas M, Jin X, Zhao X, Rui X, Ye Z, Li Y, Zhang F, Xu Q. Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of <i>Angptl3</i>. Proc Natl Acad Sci U S A. 2021;118: e2020401118. https://doi.org/10.1073/pnas.2020401118.CrossRefPubMedPubMedCentral Qiu M, Glass Z, Chen J, Haas M, Jin X, Zhao X, Rui X, Ye Z, Li Y, Zhang F, Xu Q. Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of <i>Angptl3</i>. Proc Natl Acad Sci U S A. 2021;118: e2020401118. https://​doi.​org/​10.​1073/​pnas.​2020401118.CrossRefPubMedPubMedCentral

go back to reference Chadwick AC, Evitt NH, Lv W, Musunuru K. Reduced blood lipid levels with in vivo CRISPR-Cas9 base editing of ANGPTL3. Circulation. 2018;137:975–7. https://doi.org/10.1161/CIRCULATIONAHA.117.031335.CrossRefPubMedPubMedCentral Chadwick AC, Evitt NH, Lv W, Musunuru K. Reduced blood lipid levels with in vivo CRISPR-Cas9 base editing of ANGPTL3. Circulation. 2018;137:975–7. https://​doi.​org/​10.​1161/​CIRCULATIONAHA.​117.​031335.CrossRefPubMedPubMedCentral

go back to reference Zha Y, Lu Y, Zhang T, Yan K, Zhuang W, Liang J, Cheng Y, Wang Y. CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits. Lipids Health Dis. 2021;20:180. https://doi.org/10.1186/s12944-021-01605-7.CrossRefPubMedPubMedCentral Zha Y, Lu Y, Zhang T, Yan K, Zhuang W, Liang J, Cheng Y, Wang Y. CRISPR/Cas9-mediated knockout of APOC3 stabilizes plasma lipids and inhibits atherosclerosis in rabbits. Lipids Health Dis. 2021;20:180. https://​doi.​org/​10.​1186/​s12944-021-01605-7.CrossRefPubMedPubMedCentral

go back to reference Guo M, Xu Y, Dong Z, Zhou Z, Cong N, Gao M, Huang W, Wang Y, Liu G, Xian X. Inactivation of ApoC3 by CRISPR/Cas9 protects against atherosclerosis in hamsters. Circ Res. 2020;127:1456–8. https://doi.org/10.1161/CIRCRESAHA.120.317686.CrossRefPubMed Guo M, Xu Y, Dong Z, Zhou Z, Cong N, Gao M, Huang W, Wang Y, Liu G, Xian X. Inactivation of ApoC3 by CRISPR/Cas9 protects against atherosclerosis in hamsters. Circ Res. 2020;127:1456–8. https://​doi.​org/​10.​1161/​CIRCRESAHA.​120.​317686.CrossRefPubMed

go back to reference Arabi F, Mansouri V, Ahmadbeigi N. Gene therapy clinical trials, where do we go? An overview Biomed Pharmacother. 2022;153: 113324. https://doi.org/10.1016/j.biopha.2022.113324.CrossRefPubMed Arabi F, Mansouri V, Ahmadbeigi N. Gene therapy clinical trials, where do we go? An overview Biomed Pharmacother. 2022;153: 113324. https://​doi.​org/​10.​1016/​j.​biopha.​2022.​113324.CrossRefPubMed