HITI could be 10x more effective than CRISPR Cas9 early research shows

11/24/2016 - 17:25

Image: Salk Institute

A proof-of-concept study has shown that a new genome-editing approach not only works in nondividing cells, it also allows for the efficient and targeted insertion of genes when it is used in animal models. The new approach is called HITI, for homology-independent targeted integration.

HITI looks particularly promising because it opens a largely unused pathway to the targeted genetic revision of live adult organisms.


Ref: In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration. Nature (16 November 2016) | DOI: 10.1038/nature20565


Targeted genome editing via engineered nucleases is an exciting area of biomedical research and holds potential for clinical applications. Despite rapid advances in the field, in vivo targeted transgene integration is still infeasible because current tools are inefficient, especially for non-dividing cells, which compose most adult tissues. This poses a barrier for uncovering fundamental biological principles and developing treatments for a broad range of genetic disorders. Based on clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) technology, here we devise a homology-independent targeted integration (HITI) strategy, which allows for robust DNA knock-in in both dividing and non-dividing cells in vitro and, more importantly, in vivo (for example, in neurons of postnatal mammals). As a proof of concept of its therapeutic potential, we demonstrate the efficacy of HITI in improving visual function using a rat model of the retinal degeneration condition retinitis pigmentosa. The HITI method presented here establishes new avenues for basic research and targeted gene therapies.