In vivo versus ex vivo CRISPR therapies for retinal dystrophy

SUMMARY

Two therapeutic paths have been proposed to treat inherited retinal dystrophy using clustered regularly interspaced short palindromic repeats (CRISPR). One strategy is to genetically correct patient cells ex vivo for autologous transplant, whereas the second is to modify cells in vivo by delivering CRISPR effectors to the retina. The feasibility of both editing strategies has been demonstrated within three years of CRISPR’s adaptation to mammalian systems. However, the functional integration of transplanted cells into host retinae has been a long-standing challenge that currently represents the 2025 moonshot of the National Eye Institute’s Audacious Goals Initiative. The clinical translatability of each path is discussed with regard to current investigations and whether cell replacement can be circumvented by in vivo editing.

KEYWORDS:

• CRISPR
• gene editing
• retinal degeneration
• retinal dystrophy
• retinitis pigmentosa
• translational medicine

Acknowledgments

The author thanks Dr. Ritchie Ho and Dr. Alex Laperle for their critical review of the manuscript.

Declaration of interest

The author is listed as co-inventor by Cedars-Sinai Medical Center on Non-Provisional Patent Application 15/130,846 846 filed in the United States Patent and Trademark Office on April 15, 2016 for the use of CRISPR/Cas9 as in vivo gene therapy to generate targeted genomic disruptions in genes bearing dominant mutations for retinitis pigmentosa. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was supported by the Cedars-Sinai Medical Center’s Board of Governors Regenerative Medicine Institute.