Cell Stem Cell

Compact tool switches on multiple genes in lab-grown cells

In cell experiments, a single compact DNA construct supported simultaneous activation of up to 12 genes already present in the cells.

Paper by Zhiquan Liu, Siyu Chen, Wenmin Wang, +6 more authorsYang Sun · Stanford Medicine
Studied:
Experiments in HEK293T cells, 72 hours, against dSpCas9-based activators
What changed:
A single construct activated up to 12 endogenous genes at once, at less than half the size of dSpCas9-based activators
The catch:
Effects on aging were not measured; mouse tests used chemical injury, not degeneration
Why it’s aging research:
Repairing, replacing or regenerating the aging body.

Editor of record: Boris Djordjevic · AgingResearch.News

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Experiments in HEK293T cells grown in the lab tested a compact tool for turning on genes. Researchers developed TIGRa, a programmable gene activator, and compared it with existing systems. They measured gene activity 72 hours after introducing DNA instructions into the cells.

TIGRa was less than half the size of activators based on Cas9, a DNA-cutting protein disabled for this use, while achieving comparable or greater activation efficiency. Its compact design supported activation of up to 12 genes at once. In separate experiments, activating several genes reprogrammed human fibroblasts, cells that make connective tissue, into stem cells capable of forming many cell types. In mice with chemically induced eye injury, virus-delivered TIGRa promoted survival of retinal nerve cells and preserved visual function.

Why it matters

Cell reprogramming is relevant to regenerative research on aging tissues. The authors presented TIGRa as a platform for therapeutic gene regulation.

Caveats

These were experiments in cells and mice, not tests in people or of effects on aging. The retinal experiments used chemically induced injury in 8-week-old mice, rather than age-related degeneration.

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