This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Duan D, Goemans N, Takeda S, Mercuri E, Aartsma-Rus A. Duchenne muscular dystrophy. Nat Rev Dis Primers. 2021;7:13.
Dowling JJ, Weihl CC, Spencer MJ. Molecular and cellular basis of genetically inherited skeletal muscle disorders. Nat Rev Mol Cell Biol. 2021;22:713–32.
Broomfield J, Hill M, Guglieri M, Crowther M, Abrams K. Life expectancy in Duchenne muscular dystrophy: reproduced individual patient data meta-analysis. Neurology. 2021;97:e2304–14.
Dowling JJ, DG H, Cohn RD, Campbell C. Treating pediatric neuromuscular disorders: the future is now. Am J Med Genet A. 2018;176:804–41.
Fortunato F, Farne M, Ferlini A. The DMD gene and therapeutic approaches to restore dystrophin. Neuromuscul Disord. 2021;31:1013–20.
Dowling JJ. Eteplirsen therapy for Duchenne muscular dystrophy: skipping to the front of the line. Nat Rev Neurol. 2016;12:675–6.
Elangkovan N, Dickson G. Gene therapy for Duchenne muscular dystrophy. J Neuromuscul Dis. 2021;8:S303–16.
Aslesh T, Erkut E, Yokota T. Restoration of dystrophin expression and correction of Duchenne muscular dystrophy by genome editing. Expert Opin Biol Ther. 2021;21:1049–61.
Amoasii L, Long C, Li H, Mireault AA, Shelton JM, Sanchez-Ortiz E, et al. Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy. Sci Transl Med. 2017;9:1–11.
El Refaey M, Xu L, Gao Y, Canan BD, Adesanya TMA, Warner SC, et al. In vivo genome editing restores dystrophin expression and cardiac function in dystrophic mice. Circ Res. 2017;121:923–9.
Bengtsson NE, Hall JK, Odom GL, Phelps MP, Andrus CR, Hawkins RD, et al. Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy. Nat Commun. 2017;8:14454.
Nelson CE, Wu Y, Gemberling MP, Oliver ML, Waller MA, Bohning JD, et al. Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy. Nat Med. 2019;25:427–32.
Wojtal D, Kemaladewi DU, Malam Z, Abdullah S, Wong TW, Hyatt E, et al. Spell checking nature: versatility of CRISPR/Cas9 for developing treatments for inherited disorders. Am J Hum Genet. 2016;98:90–101.
Amoasii L, Hildyard JCW, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, et al. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science. 2018;362:86–91.
Zuccaro MV, Xu J, Mitchell C, Marin D, Zimmerman R, Rana B, et al. Allele-specific chromosome removal after Cas9 cleavage in human embryos. Cell. 2020;183:1650–64.e15.
Kosicki M, Tomberg K, Bradley A. Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements. Nat Biotechnol. 2018;36:765–71.
Shin HY, Wang C, Lee HK, Yoo KH, Zeng X, Kuhns T, et al. CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome. Nat Commun. 2017;8:15464.
Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, Gray SJ, Kay CN, et al. Current clinical applications of In vivo gene therapy with AAVs. Mol Ther. 2021;29:464–88.
Hakim CH, Kumar SRP, Perez-Lopez DO, Wasala NB, Zhang D, Yue Y, et al. Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models. Nat Commun. 2021;12:6769.
Li A, Tanner MR, Lee CM, Hurley AE, De Giorgi M, Jarrett KE, et al. AAV-CRISPR gene editing is negated by pre-existing immunity to Cas9. Mol Ther. 2020;28:1432–41.
Simhadri VL, McGill J, McMahon S, Wang J, Jiang H, Sauna ZE. Prevalence of pre-existing antibodies to CRISPR-associated nuclease Cas9 in the USA population. Mol Ther Methods Clin Dev. 2018;10:105–12.
Charlesworth CT, Deshpande PS, Dever DP, Camarena J, Lemgart VT, Cromer MK, et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat Med. 2019;25:249–54.
Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia. N Engl J Med. 2021;384:252–60.
Wagner DL, Peter L, Schmueck-Henneresse M. Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy? Gene Ther. 2021;28:549–59.
Gough V, Gersbach CA. Immunity to Cas9 as an obstacle to persistent genome editing. Mol Ther. 2020;28:1389–91.
Acknowledgements
The author thanks Zachary Coulson for generating the figure, and for helpful review of the manuscript.
Author information
Authors and Affiliations
Contributions
JJD conceived, wrote, edited, and finalized all aspects of this manuscript. Zachary Coulson helped generated the figure (see acknowledgements).
Corresponding author
Ethics declarations
Competing interests
The author declares no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Dowling, J.J. CRISPR editing as a therapeutic strategy for Duchenne muscular dystrophy—anti-Cas9 immune response casts its shadow over safety and efficacy. Gene Ther 29, 575–577 (2022). https://doi.org/10.1038/s41434-022-00323-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41434-022-00323-8