15 May 2019
Vol 11, Issue 492

About The Cover

Cover image expansion

ONLINE COVER Going Big in Gene Therapy. The image shows a three-dimensional human retinal organoid co-transduced by two adeno-associated viral (AAV) vectors. Tornabene et al. tested the efficiency of producing large proteins using AAV split intein-mediated protein trans-splicing to treat inherited retinal diseases. Inteins are protein segments that self-excise and rearrange spontaneously into large proteins. The AAV vectors were safe and improved the phenotypes of mouse models of Stargardt disease and Leber congenital amaurosis type 10. These findings support the therapeutic potential of AAV intein vectors for gene therapy of blinding diseases due to mutations in large genes. [CREDIT: TORNABENE ET AL./SCIENCE TRANSLATIONAL MEDICINE]