Research ArticleGene Therapy

Intein-mediated protein trans-splicing expands adeno-associated virus transfer capacity in the retina

See allHide authors and affiliations

Science Translational Medicine  15 May 2019:
Vol. 11, Issue 492, eaav4523
DOI: 10.1126/scitranslmed.aav4523

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Leveraging naturally occurring splicing for gene therapy

Retinal gene therapy using adeno-associated viral (AAV) vectors has been shown to be effective in a number of eye diseases. However, the limited capacity of AAV hampers the use of gene therapy for delivering large genes. Now, Tornabene et al. leveraged the properties of genetic elements called split inteins to deliver large genes using multiple vectors. In unicellular organisms, split inteins mediate the fusion of two separate peptides. Here, the authors were able to reconstitute large full-length proteins using split inteins in vitro in pig retina and human organoids and in vivo in two mouse models of inherited retinal diseases with high efficiency, obtaining therapeutic effects.