Related Experiment Videos
TIGRa: An ultra-compact programmable activator enabling multiplexed and efficient gene regulation
Zhiquan Liu1, Siyu Chen1, Wenmin Wang1
1Department of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Cell Stem Cell
|August 10, 2026
Summary
We developed TIGRa, a compact gene activator smaller than CRISPR systems, enabling simultaneous activation of multiple genes. This platform shows promise for reprogramming cells and treating eye injuries in vivo.
Area of Science:
- Molecular Biology
- Gene Regulation
- Synthetic Biology
Background:
- Programmable gene activation is crucial for therapeutics but hindered by large effector size and limited multiplexing.
- Existing systems like CRISPR-based activators face challenges in size, delivery, and multiplexing capacity.
Purpose of the Study:
- To develop a compact and multiplexable transcriptional activator for gene regulation.
- To evaluate the efficacy of the TIGRa system for cellular reprogramming and in vivo gene therapy.
Main Methods:
- Developed TIGRa, a compact transcriptional activator based on the TIGR-TasR system.
- Assessed TIGRa's size, activation efficiency, and multiplexing capacity compared to dSpCas9 activators.
- Utilized TIGRa for reprogramming human fibroblasts and for in vivo gene activation via AAV delivery.
Main Results:
- TIGRa is less than half the size of dSpCas9 activators with comparable or greater activation efficiency.
- TIGRa enables multiplexed regulation of up to 12 endogenous genes from a single construct.
- TIGRa successfully reprogrammed fibroblasts into induced pluripotent stem cells and promoted retinal cell survival in vivo.
Conclusions:
- TIGRa is a compact and highly multiplexable platform for gene regulation.
- The TIGRa system offers a promising tool for therapeutic gene regulation and in vivo genetic medicine.