Clustered regularly interspaced short palindromic repeats strategies for the treatment of genetic eye diseases
TL;DR
It was concluded that these technologies surpass the biological efficiency thresholds necessary to halt retinal degeneration and are established not as universal solutions, but as complementary tools whose selection depends strictly on the genetic architecture of the pathology.
Abstract
Inherited retinal diseases (IRDs) have historically represented a significant therapeutic challenge due to the cargo capacity and durability limitations of traditional gene replacement therapy, especially for large or complex genes. The main objective of this research was to evaluate the translational potential of advanced genome editing technologies to overcome such barriers. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 methodology guidelines from January 2020 to November 2025; the search was performed in PubMed and Google Scholar, complemented by Rayyan for the removal of duplicates. Preclinical studies contrasting reading frame restoration (NHEJ), homology-independent targeted integration (HITI), and base editing (BE) were included. The results revealed that BE established itself as the safest and most precise strategy for correcting point mutations by avoiding double-strand breaks (DSBs) in DNA, thereby preserving photoreceptor integrity. Conversely, HITI proved to be indispensable for the insertion of complete therapeutic exons in complex genes, despite challenges such as unwanted viral insertions. It was concluded that these technologies surpass the biological efficiency thresholds necessary to halt retinal degeneration. They are established not as universal solutions, but as complementary tools whose selection depends strictly on the genetic architecture of the pathology.
