Gene therapy for monogenic disorders: challenges, strategies, and perspectives

Yi Zhang; Zhi-Ying Wu

doi:10.1016/j.jgg.2023.08.001

Volume 51 Issue 2

Feb. 2024

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2024 > 51(2): 133-143

PDF( 1128 KB)

Gene therapy for monogenic disorders: challenges, strategies, and perspectives

doi: 10.1016/j.jgg.2023.08.001

Yi Zhang^a,b,c,
Zhi-Ying Wu^a,b,c

a. Department of Medical Genetics and Center for Rare Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China;
b. Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China;
c. Key Laboratory of Medical Neurobiology of Zhejiang Province, Hangzhou, Zhejiang 310009, China

Funds:

We are grateful to Prof. Aaron D. Gitler for his contribution to the proofreading and grammatical editing of this manuscript. We thank Dr. Hai-Lin Dong for suggesting revisions to the manuscript.

Received Date: 2023-06-03
Accepted Date: 2023-08-05
Rev Recd Date: 2023-08-02
Publish Date: 2023-08-14

Abstract

Abstract

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.
- Gene therapy,
- Monogenic diseases,
- Gene editing,
- Gene delivery,
- Challenges

FullText(HTML)

References(103)

References

Anguela, X.M., High, K.A., 2019. Entering the modern era of gene therapy. Annu. Rev. Med. 70, 273-288.

Anzalone, A.V., Randolph, P.B., Davis, J.R., Sousa, A.A., Koblan, L.W., Levy, J.M., Chen, P.J., Wilson, C., Newby, G.A., Raguram, A., et al., 2019. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149-157.

Arbab, M., Matuszek, Z., Kray, K.M., Du, A., Newby, G.A., Blatnik, A.J., Raguram, A., Richter, M.F., Zhao, K.T., Levy, J.M., et al., 2023. Base editing rescue of spinal muscular atrophy in cells and in mice. Science 380, eadg6518.

Banskota, S., Raguram, A., Suh, S., Du, S.W., Davis, J.R., Choi, E.H., Wang, X., Nielsen, S.C., Newby, G.A., Randolph, P.B., et al., 2022. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins. Cell 185, 250-265.

Bertolini, T.B., Shirley, J.L., Zolotukhin, I., Li, X., Kaisho, T., Xiao, W., Kumar, S.R.P., Herzog, R.W., 2021. Effect of CpG depletion of vector genome on CD8(+) T cell responses in AAV gene therapy. Front. Immunol. 12, 672449.

Bot, J.F., van der Oost, J., Geijsen, N., 2022. The double life of CRISPR-Cas13. Curr. Opin. Biotechnol. 78, 102789.

Bravo, J.P.K., Liu, M.S., Hibshman, G.N., Dangerfield, T.L., Jung, K., McCool, R.S., Johnson, K.A., Taylor, D.W., 2022. Structural basis for mismatch surveillance by CRISPR-Cas9. Nature 603, 343-347.

Cecchin, R., Troyer, Z., Witwer, K., Morris, K.V., 2023. Extracellular vesicles: the next generation in gene therapy delivery. Mol. Ther. 31, 1225-1230.

Chan, Y.K., Wang, S.K., Chu, C.J., Copland, D.A., Letizia, A.J., Costa Verdera, H., Chiang, J.J., Sethi, M., Wang, M.K., Neidermyer, W.J., Jr., et al., 2021. Engineering adeno-associated viral vectors to evade innate immune and inflammatory responses. Sci. Transl. Med. 13, eabd3438.

Chemello, F., Chai, A.C., Li, H., Rodriguez-Caycedo, C., Sanchez-Ortiz, E., Atmanli, A., Mireault, A.A., Liu, N., Bassel-Duby, R., Olson, E.N., 2021. Precise correction of Duchenne muscular dystrophy exon deletion mutations by base and prime editing. Sci. Adv. 7, eabg4910.

Chen, L., Zhang, S., Xue, N., Hong, M., Zhang, X., Zhang, D., Yang, J., Bai, S., Huang, Y., Meng, H., et al., 2023. Engineering a precise adenine base editor with minimal bystander editing. Nat. Chem. Biol. 19, 101-110.

Chen, L., Zhu, B., Ru, G., Meng, H., Yan, Y., Hong, M., Zhang, D., Luan, C., Zhang, S., Wu, H., et al., 2022a. Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nat. Biotechnol. 41, 663-672.

Chen, P.J., Hussmann, J.A., Yan, J., Knipping, F., Ravisankar, P., Chen, P.F., Chen, C., Nelson, J.W., Newby, G.A., Sahin, M., et al., 2021. Enhanced prime editing systems by manipulating cellular determinants of editing outcomes. Cell 184, 5635-5652.

Chen, W., Hu, Y., Ju, D., 2020. Gene therapy for neurodegenerative disorders: advances, insights and prospects. Acta Pharm. Sin. B 10, 1347-1359.

Chen, Y.L., Chen, D.F., Li, H.F., Wu, Z.Y., 2022b. Features differ between paroxysmal kinesigenic dyskinesia patients with PRRT2 and TMEM151A variants. Mov. Disord. 37, 608-613.

Cheng, Q., Wei, T., Farbiak, L., Johnson, L.T., Dilliard, S.A., Siegwart, D.J., 2020. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat. Nanotechnol. 15, 313-320.

Clemens, P.R., Rao, V.K., Connolly, A.M., Harper, A.D., Mah, J.K., Smith, E.C., McDonald, C.M., Zaidman, C.M., Morgenroth, L.P., Osaki, H., et al., 2020. Safety, tolerability, and efficacy of viltolarsen in boys with Duchenne muscular dystrophy amenable to exon 53 skipping: a phase 2 randomized clinical trial. JAMA Neurol. 77, 982-991.

Dautzenberg, I.J.C., Rabelink, M., Hoeben, R.C., 2021. The stability of envelope-pseudotyped lentiviral vectors. Gene Ther. 28, 89-104.

Davis, J.R., Wang, X., Witte, I.P., Huang, T.P., Levy, J.M., Raguram, A., Banskota, S., Seidah, N.G., Musunuru, K., Liu, D.R., 2022. Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors. Nat. Biomed. Eng. 6, 1272-1283.

Dong, Y., Wu, Z.Y., 2021. Challenges and suggestions for precise diagnosis and treatment of Wilson's disease. World J. Pediatr. 17, 561-565.

Duan, D., Goemans, N., Takeda, S., Mercuri, E., Aartsma-Rus, A., 2021. Duchenne muscular dystrophy. Nat. Rev. Dis. Prim. 7, 13.

Dunbar, C.E., High, K.A., Joung, J.K., Kohn, D.B., Ozawa, K., Sadelain, M., 2018. Gene therapy comes of age. Science 359, eaan4672.

Edraki, A., Mir, A., Ibraheim, R., Gainetdinov, I., Yoon, Y., Song, C.Q., Cao, Y., Gallant, J., Xue, W., Rivera-Perez, J.A., et al., 2019. A compact, high-accuracy Cas9 with a dinucleotide PAM for in vivo genome editing. Mol. Cell 73, 714-726.

Esposito, F., Lyubenova, H., Tornabene, P., Auricchio, S., Iuliano, A., Nusco, E., Merlin, S., Olgasi, C., Manni, G., Gargaro, M., et al., 2022. Liver gene therapy with intein-mediated F8 trans-splicing corrects mouse haemophilia A. EMBO Mol. Med. 14, e15199.

Evers, M.M., Miniarikova, J., Juhas, S., Valles, A., Bohuslavova, B., Juhasova, J., Skalnikova, H.K., Vodicka, P., Valekova, I., Brouwers, C., et al., 2018. AAV5-miHTT gene therapy demonstrates broad distribution and strong human mutant huntingtin lowering in a Huntington's disease minipig model. Mol. Ther. 26, 2163-2177.

Fitzgerald, K., White, S., Borodovsky, A., Bettencourt, B.R., Strahs, A., Clausen, V., Wijngaard, P., Horton, J.D., Taubel, J., Brooks, A., et al., 2017. A highly durable RNAi therapeutic inhibitor of PCSK9. N. Engl. J. Med. 376, 41-51.

Francis, J.S., Markov, V., Wojtas, I.D., Gray, S., McCown, T., Samulski, R.J., Figueroa, M., Leone, P., 2021. Preclinical biodistribution, tropism, and efficacy of oligotroph AAV/Olig001 in a mouse model of congenital white matter disease. Mol. Ther. Methods Clin. Dev. 20, 520-534.

Frank, D.E., Schnell, F.J., Akana, C., El-Husayni, S.H., Desjardins, C.A., Morgan, J., Charleston, J.S., Sardone, V., Domingos, J., Dickson, G., et al., 2020. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology 94, e2270-e2282.

Friedmann, T., Roblin, R., 1972. Gene therapy for human genetic disease? Science 175, 949-955.

Gao, X., Tao, Y., Lamas, V., Huang, M., Yeh, W.H., Pan, B., Hu, Y.J., Hu, J.H., Thompson, D.B., Shu, Y., et al., 2018. Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents. Nature 553, 217-221.

Gillmore, J.D., Gane, E., Taubel, J., Kao, J., Fontana, M., Maitland, M.L., Seitzer, J., O'Connell, D., Walsh, K.R., Wood, K., et al., 2021. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493-502.

Gokirmak, T., Nikan, M., Wiechmann, S., Prakash, T.P., Tanowitz, M., Seth, P.P., 2021. Overcoming the challenges of tissue delivery for oligonucleotide therapeutics. Trends Pharmacol. Sci. 42, 588-604.

Hamimed, S., Jabberi, M., Chatti, A., 2022. Nanotechnology in drug and gene delivery. Naunyn-Schmiedeberg’s Arch. Pharmacol. 395, 769-787.

Haraszti, R.A., Roux, L., Coles, A.H., Turanov, A.A., Alterman, J.F., Echeverria, D., Godinho, B., Aronin, N., Khvorova, A., 2017. 5΄-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo. Nucleic Acids Res. 45, 7581-7592.

Hu, Z., Zhang, C., Wang, S., Gao, S., Wei, J., Li, M., Hou, L., Mao, H., Wei, Y., Qi, T., et al., 2021. Discovery and engineering of small SlugCas9 with broad targeting range and high specificity and activity. Nucleic Acids Res. 49, 4008-4019.

Huang, T.P., Heins, Z.J., Miller, S.M., Wong, B.G., Balivada, P.A., Wang, T., Khalil, A.S., Liu, D.R., 2023. High-throughput continuous evolution of compact Cas9 variants targeting single-nucleotide-pyrimidine PAMs. Nat. Biotechnol. 41, 96-107.

Hull, V., Wang, Y., Burns, T., Zhang, S., Sternbach, S., McDonough, J., Guo, F., Pleasure, D., 2020. Antisense oligonucleotide reverses leukodystrophy in Canavan disease mice. Ann. Neurol. 87, 480-485.

Hussain, W., Yang, X., Ullah, M., Wang, H., Aziz, A., Xu, F., Asif, M., Ullah, M.W., Wang, S., 2023. Genetic engineering of bacteriophages: key concepts, strategies, and applications. Biotechnol. Adv. 64, 108116.

Ikwuagwu, B., Tullman-Ercek, D., 2022. Virus-like particles for drug delivery: a review of methods and applications. Curr. Opin. Biotechnol. 78, 102785.

Imbert, M., Blandel, F., Leumann, C., Garcia, L., Goyenvalle, A., 2019. Lowering mutant huntingtin using tricyclo-DNA antisense oligonucleotides as a therapeutic approach for Huntington's disease. Nucleic Acid Therapeut. 29, 256-265.

Jang, H.K., Jo, D.H., Lee, S.N., Cho, C.S., Jeong, Y.K., Jung, Y., Yu, J., Kim, J.H., Woo, J.S., Bae, S., 2021. High-purity production and precise editing of DNA base editing ribonucleoproteins. Sci. Adv. 7, eabg2661.

Jo, D.H., Jang, H.K., Cho, C.S., Han, J.H., Ryu, G., Jung, Y., Bae, S., Kim, J.H., 2023. Visual function restoration in a mouse model of Leber congenital amaurosis via therapeutic base editing. Mol. Ther. Nucleic Acids 31, 16-27.

Kalluri, R., LeBleu, V.S., 2020. The biology, function, and biomedical applications of exosomes. Science 367, eaau6977.

Kelleher, J., Dickinson, A., Cain, S., Hu, Y., Bates, N., Harvey, A., Ren, J., Zhang, W., Moreton, F.C., Muir, K.W., et al., 2019. Patient-specific iPSC model of a genetic vascular dementia syndrome reveals failure of mural cells to stabilize capillary structures. Stem Cell Rep. 13, 817-831.

Kimiz-Gebologlu, I., Oncel, S.S., 2022. Exosomes: large-scale production, isolation, drug loading efficiency, and biodistribution and uptake. J. Contr. Release 347, 533-543.

Koblan, L.W., Erdos, M.R., Wilson, C., Cabral, W.A., Levy, J.M., Xiong, Z.M., Tavarez, U.L., Davison, L.M., Gete, Y.G., Mao, X., et al., 2021. In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice. Nature 589, 608-614.

Komaki, H., Nagata, T., Saito, T., Masuda, S., Takeshita, E., Sasaki, M., Tachimori, H., Nakamura, H., Aoki, Y., Takeda, S., 2018. Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci. Transl. Med. 10, eaan0713.

Lam, D.K., Feliciano, P.R., Arif, A., Bohnuud, T., Fernandez, T.P., Gehrke, J.M., Grayson, P., Lee, K.D., Ortega, M.A., Sawyer, C., et al., 2023. Improved cytosine base editors generated from TadA variants. Nat. Biotechnol. 41, 686-697.

Levy, J.M., Yeh, W.H., Pendse, N., Davis, J.R., Hennessey, E., Butcher, R., Koblan, L.W., Comander, J., Liu, Q., Liu, D.R., 2020. Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses. Nat. Biomed. Eng. 4, 97-110.

Li, C., Georgakopoulou, A., Mishra, A., Gil, S., Hawkins, R.D., Yannaki, E., Lieber, A., 2021. In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal gamma-globin in beta-YAC mice. Blood Adv. 5, 1122-1135.

Li, C., Samulski, R.J., 2020. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 21, 255-272.

Li, J., Hong, S., Chen, W., Zuo, E., Yang, H., 2019. Advances in detecting and reducing off-target effects generated by CRISPR-mediated genome editing. J. Genet. Genomics 46, 513-521.

Li, L., Meng, H., Zhang, J., Liu, Y., Zou, Q., Gao, Y., Yang, H., Lai, L., 2020a. A tunable, rapid, and precise drug control of protein expression by combining transcriptional and post-translational regulation systems. J. Genet. Genomics 47, 705-712.

Li, X., Qian, X., Wang, B., Xia, Y., Zheng, Y., Du, L., Xu, D., Xing, D., DePinho, R.A., Lu, Z., 2020b. Programmable base editing of mutated TERT promoter inhibits brain tumour growth. Nat. Cell Biol. 22, 282-288.

Lim, C.K.W., Gapinske, M., Brooks, A.K., Woods, W.S., Powell, J.E., Zeballos, C.M., Winter, J., Perez-Pinera, P., Gaj, T., 2020. Treatment of a mouse model of ALS by in vivo base editing. Mol. Ther. 28, 1177-1189.

Luo, M., Lee, L.K.C., Peng, B., Choi, C.H.J., Tong, W.Y., Voelcker, N.H., 2022. Delivering the promise of gene therapy with nanomedicines in treating central nervous system diseases. Adv. Sci. 9, e2201740.

Maguire, A.M., Russell, S., Wellman, J.A., Chung, D.C., Yu, Z.F., Tillman, A., Wittes, J., Pappas, J., Elci, O., Marshall, K.A., et al., 2019. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology 126, 1273-1285.

Martier, R., Liefhebber, J.M., Garcia-Osta, A., Miniarikova, J., Cuadrado-Tejedor, M., Espelosin, M., Ursua, S., Petry, H., van Deventer, S.J., Evers, M.M., et al., 2019a. Targeting RNA-mediated toxicity in C9orf72 ALS and/or FTD by RNAi-based gene therapy. Mol. Ther. Nucleic Acids 16, 26-37.

Martier, R., Liefhebber, J.M., Miniarikova, J., van der Zon, T., Snapper, J., Kolder, I., Petry, H., van Deventer, S.J., Evers, M.M., Konstantinova, P., 2019b. Artificial microRNAs targeting C9orf72 can reduce accumulation of intra-nuclear transcripts in ALS and FTD patients. Mol. Ther. Nucleic Acids 14, 593-608.

Mendell, J.R., Al-Zaidy, S., Shell, R., Arnold, W.D., Rodino-Klapac, L.R., Prior, T.W., Lowes, L., Alfano, L., Berry, K., Church, K., et al., 2017. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 377, 1713-1722.

Mendell, J.R., Goemans, N., Lowes, L.P., Alfano, L.N., Berry, K., Shao, J., Kaye, E.M., Mercuri, E., Eteplirsen Study, G., Telethon Foundation, D.M.D.I.N., 2016. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann. Neurol. 79, 257-271.

Mendell, J.R., Sahenk, Z., Lehman, K., Nease, C., Lowes, L.P., Miller, N.F., Iammarino, M.A., Alfano, L.N., Nicholl, A., Al-Zaidy, S., et al., 2020. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a monrandomized controlled trial. JAMA Neurol. 77, 1122-1131.

Mercuri, E., Sumner, C.J., Muntoni, F., Darras, B.T., Finkel, R.S., 2022. Spinal muscular atrophy. Nat. Rev. Dis. Prim. 8, 52.

Miesbach, W., Meijer, K., Coppens, M., Kampmann, P., Klamroth, R., Schutgens, R., Tangelder, M., Castaman, G., Schwable, J., Bonig, H., et al., 2018. Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B. Blood 131, 1022-1031.

Mietzsch, M., Barnes, C., Hull, J.A., Chipman, P., Xie, J., Bhattacharya, N., Sousa, D., McKenna, R., Gao, G., Agbandje-McKenna, M., 2020. Comparative analysis of the capsid structures of AAVrh.10, AAVrh.39, and AAV8. J. Virol. 94, e01769-e01719.

Miller, T.M., Cudkowicz, M.E., Genge, A., Shaw, P.J., Sobue, G., Bucelli, R.C., Chio, A., Van Damme, P., Ludolph, A.C., Glass, J.D., et al., 2022. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N. Engl. J. Med. 387, 1099-1110.

Mitchell, M.J., Billingsley, M.M., Haley, R.M., Wechsler, M.E., Peppas, N.A., Langer, R., 2021. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20, 101-124.

Monteys, A.M., Hundley, A.A., Ranum, P.T., Tecedor, L., Muehlmatt, A., Lim, E., Lukashev, D., Sivasankaran, R., Davidson, B.L., 2021. Regulated control of gene therapies by drug-induced splicing. Nature 596, 291-295.

Moreira, A.S., Cavaco, D.G., Faria, T.Q., Alves, P.M., Carrondo, M.J.T., Peixoto, C., 2021. Advances in lentivirus purification. Biotechnol. J. 16, e2000019.

Mueller, C., Berry, J.D., McKenna-Yasek, D.M., Gernoux, G., Owegi, M.A., Pothier, L.M., Douthwright, C.L., Gelevski, D., Luppino, S.D., Blackwood, M., et al., 2020. SOD1 suppression with adeno-associated virus and microRNA in familial ALS. N. Engl. J. Med. 383, 151-158.

Muhuri, M., Maeda, Y., Ma, H., Ram, S., Fitzgerald, K.A., Tai, P.W., Gao, G., 2021. Overcoming innate immune barriers that impede AAV gene therapy vectors. J. Clin. Invest. 131, e143780.

Musunuru, K., Chadwick, A.C., Mizoguchi, T., Garcia, S.P., DeNizio, J.E., Reiss, C.W., Wang, K., Iyer, S., Dutta, C., Clendaniel, V., et al., 2021. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593, 429-434.

Nagata, T., Dwyer, C.A., Yoshida-Tanaka, K., Ihara, K., Ohyagi, M., Kaburagi, H., Miyata, H., Ebihara, S., Yoshioka, K., Ishii, T., et al., 2021. Cholesterol-functionalized DNA/RNA heteroduplexes cross the blood-brain barrier and knock down genes in the rodent CNS. Nat. Biotechnol. 39, 1529-1536.

Pacesa, M., Lin, C.H., Clery, A., Saha, A., Arantes, P.R., Bargsten, K., Irby, M.J., Allain, F.H., Palermo, G., Cameron, P., et al., 2022. Structural basis for Cas9 off-target activity. Cell 185, 4067-4081.

Padula, A., Petruzzelli, R., Philbert, S.A., Church, S.J., Esposito, F., Campione, S., Monti, M., Capolongo, F., Perna, C., Nusco, E., et al., 2022. Full-length ATP7B reconstituted through protein trans-splicing corrects Wilson disease in mice. Mol. Ther. Methods Clin. Dev. 26, 495-504.

Paunovska, K., Loughrey, D., Dahlman, J.E., 2022. Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 23, 265-280.

Petrich, J., Marchese, D., Jenkins, C., Storey, M., Blind, J., 2020. Gene replacement therapy: a primer for the health-system pharmacist. J. Pharm. Pract. 33, 846-855.

Raguram, A., Banskota, S., Liu, D.R., 2022. Therapeutic in vivo delivery of gene editing agents. Cell 185, 2806-2827.

Ravi, B., Chan-Cortes, M.H., Sumner, C.J., 2021. Gene-targeting therapeutics for neurological disease: lessons learned from spinal muscular atrophy. Annu. Rev. Med. 72, 1-14.

Rees, H.A., Liu, D.R., 2018. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770-788.

Roberts, T.C., Langer, R., Wood, M.J.A., 2020. Advances in oligonucleotide drug delivery. Nat. Rev. Drug Discov. 19, 673-694.

Roth, T.L., Marson, A., 2021. Genetic disease and therapy. Annu. Rev. Pathol. 16, 145-166.

Rothgangl, T., Dennis, M.K., Lin, P.J.C., Oka, R., Witzigmann, D., Villiger, L., Qi, W., Hruzova, M., Kissling, L., Lenggenhager, D., et al., 2021. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat. Biotechnol. 39, 949-957.

Sardh, E., Harper, P., Balwani, M., Stein, P., Rees, D., Bissell, D.M., Desnick, R., Parker, C., Phillips, J., Bonkovsky, H.L., et al., 2019. Phase 1 trial of an RNA interference therapy for acute intermittent porphyria. N. Engl. J. Med. 380, 549-558.

Scharner, J., Aznarez, I., 2021. Clinical applications of single-stranded oligonucleotides: current landscape of approved and in-development therapeutics. Mol. Ther. 29, 540-554.

Schuler, G., Hu, C., Ke, A., 2022. Structural basis for RNA-guided DNA cleavage by IscB-omegaRNA and mechanistic comparison with Cas9. Science 376, 1476-1481.

Suh, S., Choi, E.H., Leinonen, H., Foik, A.T., Newby, G.A., Yeh, W.H., Dong, Z., Kiser, P.D., Lyon, D.C., Liu, D.R., et al., 2021. Restoration of visual function in adult mice with an inherited retinal disease via adenine base editing. Nat. Biomed. Eng. 5, 169-178.

Sun, J., Roy, S., 2021. Gene-based therapies for neurodegenerative diseases. Nat. Neurosci. 24, 297-311.

Tabrizi, S.J., Leavitt, B.R., Landwehrmeyer, G.B., Wild, E.J., Saft, C., Barker, R.A., Blair, N.F., Craufurd, D., Priller, J., Rickards, H., et al., 2019. Targeting huntingtin expression in patients with Huntington's disease. N. Engl. J. Med. 380, 2307-2316.

Tai, W., 2019. Current aspects of siRNA bioconjugate for in vitro and in vivo delivery. Molecules 24, 2211.

Tornabene, P., Trapani, I., Minopoli, R., Centrulo, M., Lupo, M., de Simone, S., Tiberi, P., Dell'Aquila, F., Marrocco, E., Iodice, C., et al., 2019. Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina. Sci. Transl. Med. 11, eaav4523.

Tran, H., Moazami, M.P., Yang, H., McKenna-Yasek, D., Douthwright, C.L., Pinto, C., Metterville, J., Shin, M., Sanil, N., Dooley, C., et al., 2022. Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide. Nat. Med. 28, 117-124.

Verdera, H.C., Kuranda, K., Mingozzi, F., 2020. AAV vector immunogenicity in humans: a long journey to successful gene transfer. Mol. Ther. 28, 723-746.

Von Drygalski, A., Giermasz, A., Castaman, G., Key, N.S., Lattimore, S., Leebeek, F.W.G., Miesbach, W., Recht, M., Long, A., Gut, R., et al., 2019. Etranacogene dezaparvovec (AMT-061 phase 2b): normal/near normal FIX activity and bleed cessation in hemophilia B. Blood Adv. 3, 3241-3247.

Wagner, K.R., Kuntz, N.L., Koenig, E., East, L., Upadhyay, S., Han, B., Shieh, P.B., 2021. Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: a randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve 64, 285-292.

Wang, D., Tai, P.W.L., Gao, G., 2019. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 18, 358-378.

Wang, D., Zhang, F., Gao, G., 2020. CRISPR-based therapeutic genome editing: strategies and in vivo delivery by AAV vectors. Cell 181, 136-150.

Wang, L., Xue, W., Zhang, H., Gao, R., Qiu, H., Wei, J., Zhou, L., Lei, Y.N., Wu, X., Li, X., et al., 2021. Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat. Cell Biol. 23, 552-563.

Weissbach, A., Pauly, M.G., Herzog, R., Hahn, L., Halmans, S., Hamami, F., Bolte, C., Camargos, S., Jeon, B., Kurian, M.A., et al., 2022. Relationship of genotype, phenotype, and treatment in dopa-responsive dystonia: MDSGene review. Mov. Disord. 37, 237-252.

Wilson, J.M., Flotte, T.R., 2020. Moving forward after two deaths in a gene therapy trial of myotubular myopathy. Hum. Gene Ther. 31, 695-696.

Yang, S., Chang, R., Yang, H., Zhao, T., Hong, Y., Kong, H.E., Sun, X., Qin, Z., Jin, P., Li, S., et al., 2017. CRISPR/Cas9-mediated gene editing ameliorates neurotoxicity in mouse model of Huntington's disease. J. Clin. Invest. 127, 2719-2724.

Yin, H., Song, C.Q., Suresh, S., Wu, Q., Walsh, S., Rhym, L.H., Mintzer, E., Bolukbasi, M.F., Zhu, L.J., Kauffman, K., et al., 2017. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Nat. Biotechnol. 35, 1179-1187.

Zhu, D., Schieferecke, A.J., Lopez, P.A., Schaffer, D.V., 2021. Adeno-associated virus vector for central nervous system gene therapy. Trends Mol. Med. 27, 524-537.

Relative Articles

Supplements(0)

Cited By

Proportional views