Longevity & AgingUltra-compact TIGRa gene activator switches on multiple genes from one AAV vector
Turning on several protective genes at once is attractive for diseases like glaucoma, but CRISPR-based activators are too big to fit in a single AAV vector. Researchers screened miniature RNA-guided proteins and built TIGRa from the ~300-amino-acid TasR protein, which processes its own short guide array. Fused to compact activation domains, TIGRa matched or approached dSpCas9 activators in cell culture while being far smaller. Engineered variants (Mini, Pro, Ultra) trade size against potency. According to the abstract, TIGRa activated up to 12 genes from one construct, helped reprogram human fibroblasts into iPSCs, and, delivered by a single AAV, activated CaMKII to protect retinal ganglion cells and preserve vision in a mouse injury model. The work is preclinical, but it offers a compact, multiplexable platform for gene regulation therapies.
