Evidence map›Paper›PMID 42575098›Full record

ArticleCell stem cell2026

TIGRa: An ultra-compact programmable activator enabling multiplexed and efficient gene regulation.

Zhiquan Liu, Siyu Chen, Wenmin Wang, Fan Zhang, Qing Wang, Grzegorz Walkiewicz, Faruk Hossen, Jinqiong Zhou, Yiting Wang, Yang Sun

Abstract read
In one paragraph

Article in Cell stem cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Zhiquan LiuDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA. Electronic address: zhiquan1@stanford.edu.
Siyu ChenDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Wenmin WangDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Fan ZhangDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Qing WangDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Grzegorz WalkiewiczDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Faruk HossenDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Jinqiong ZhouDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Yiting WangDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Yang SunDepartment of Ophthalmology, Stanford University School of Medicine, 1651 Page Mill Road, Palo Alto, CA 94304, USA; Palo Alto Veterans Administration, Palo Alto, CA, USA. Electronic address: yangsun@stanford.edu.

Funding

The role of primary cilia in glaucoma pathogenesisR01EY025295 · NEI · STANFORD UNIVERSITY · PI Yang Sun · 2016 to 2026
$3.5M
Phosphoinositide signaling in glaucoma: rescue strategies for Lowe syndromeR01EY032159 · NEI · STANFORD UNIVERSITY · PI SUN, YANG · 2021 to 2024
$1.6M
Novel Pathogenic Mechanisms of Joubert SyndromeR01EY036685 · NEI · STANFORD UNIVERSITY · PI Yang Sun · 2025 to 2026
$1.4M
Stanford Ophthalmology Advanced Research ProgramR38EY037090 · NEI · STANFORD UNIVERSITY · PI Yang Sun · 2025 to 2026
$495k
BLRD VA I01 BX006638CSRD VA I01 CX001481NEI NIH HHS R01 EY025295NEI NIH HHS R01 EY032159NEI NIH HHS R01 EY036685NEI NIH HHS R38 EY037090
6 · The paper itself

Abstract

Programmable gene activation has broad therapeutic potential but remains constrained by the large effector size, limited multiplexing capacity, and challenges in in vivo delivery. Here, we develop the TIGR-TasR-mediated activator (TIGRa), a compact transcriptional activator derived from the tandem interspaced guide RNA (TIGR)-TIGR-associated protein (TasR) system that is mechanistically distinct from CRISPR-based activators. TIGRa is less than half the size of dSpCas9-based activators while achieving comparable or greater activation efficiency. Its native TIGR array architecture enables efficient multiplexed regulation, supporting simultaneous activation of up to 12 endogenous genes from a single compact construct. TIGRa-mediated multi-gene activation efficiently reprogrammed human fibroblasts into induced pluripotent stem cells. In addition, an all-in-one adeno-associated virus (AAV)-TIGRa vector activated endogenous CaMKII in vivo, promoting retinal ganglion cell survival and preserving visual function in a mouse model of N-methyl-D-aspartic (NMDA)-induced retinal injury. These results establish TIGRa as a compact and multiplexable platform for therapeutic gene regulation and in vivo genetic medicine.

Indexed as

Gene Expression RegulationAnimalsDependovirusFibroblastsHumansInduced Pluripotent Stem CellsMiceRetinal Ganglion CellsTranscriptional ActivationAAV deliveryCRISPR activationgene therapyglaucomamultiplexed activationRGC protectionTIGRaTIGR arrayTIGR-TasRtranscriptional activator

Identifiers

PMID42575098
PMCPMC13526431

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.