Evidence map›Paper›PMID 42559426›Full record

ArticleTheranostics2026

Programmable transcriptional condensates for enhanced CRISPR-based gene regulation.

Aolin Li, Congcong Cao, Chunyan Yang, Yuchen Liu

Abstract read
In one paragraph

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

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0citing papers in PubMed
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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

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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

4 authors.

Aolin LiShenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518035, China.
Congcong CaoSchool of Basic Medical Sciences, Hubei University of Chinese Medicine, Hubei Shizhen Laboratory, Wuhan 430065, China.
Chunyan YangShenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518035, China.
Yuchen LiuShenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518035, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rationale: Efficient gene activation or repression through programmable CRISPR-Cas9 has revolutionized molecular biology and drug development. Nonetheless, the currently available CRISPRa/i approaches are modestly potent and require multi-component delivery, which hampers the wide use of the technology in both research and therapy. Methods: We developed a modular CRISPR-condensate platform by appending a multivalent RNA nanostar to the 3' end of a single-guide RNA, producing a sgRNA-nanostar chimera that mediates phase separation at Cas9-bound genomic loci. The nanostar scaffold also contains MS2 stem-loops, which recruit MCP-tagged transcriptional effectors (VP64 for activation, KRAB for repression) to the condensate microenvironment at high local concentration. We examined condensate formation, genome targeting, and transcriptional output by using live-cell imaging, RT-qPCR, ChIP-seq, RNA-seq and CUT&Tag in HEK293T, HeLa, U-2 OS, MDA-MB-231, as well as human iPSC cell lines. Results: The CRISPR-condensate design resulted in up to 50-100-fold target-gene activation, compared with 5-10-fold activation by direct VP64 fusion, and 20-30-fold transcriptional repression, compared with 3-5-fold repression by direct KRAB fusion, with high target specificity (12 versus 28 non-target differentially expressed genes assessed by RNA-seq). Orthogonal kissing-loop (KL) pairings enabled independent condensate systems for simultaneous activation and repression of multiplexed targets. Janus condensates containing both activating and repressive domains enabled bidirectional regulation at a single locus. The system requires delivery of only three independently expressible components-dCas9-NLS, an sgRNA-nanostar chimera bearing MS2 stem-loops (MS2SLs), and an MCP-fused effector (VP64-MCP for activation or KRAB-MCP for repression)-and showed minimal innate immune response and high cell viability. Conclusions: The CRISPR-condensate system merges the dramatically enhanced transcriptional efficacy with the reduced complexity of components, providing a modular system for fine-tuned gene expression regulation. This strategy makes biomolecular condensation a general principle for enhancing CRISPR gene regulation, opening up possibilities for functional genomics, cell engineering, and therapy development.

Indexed as

CRISPR-Cas SystemsGene EditingGene Expression RegulationClustered Regularly Interspaced Short Palindromic RepeatsHEK293 CellsHeLa CellsHumansRNA, Guide, CRISPR-Cas SystemsTranscription, GeneticRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID42559426
PMCPMC13440432

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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.