Evidence map›Paper›PMID 39820813›Full record

ArticleNature biotechnology2025

Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy.

Feifei Zhang, Ryan D Chow, Emily He, Chuanpeng Dong, Shan Xin, Daniyal Mirza, Yanzhi Feng, Xiaolong Tian, Nipun Verma, Medha Majety and 3 more

Erratum issuedAbstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Frontiers in immunology · 2026
    Review
  8. CRISPR-epigenetic crosstalk: From bidirectional regulation to therapeutic potential.Computational and structural biotechnology journal · 2025
    Review
  9. Review
  10. Review
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Feifei Zhang *Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Ryan D Chow *Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-1872-6307
Emily HeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Chuanpeng DongDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Shan XinDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4735-0935
Daniyal MirzaDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Yanzhi FengDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Xiaolong TianDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Nipun VermaDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Medha MajetyDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Yueqi ZhangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Guangchuan WangDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. guangchuan.wang@sibcb.ac.cn.ORCID http://orcid.org/0000-0001-5315-1599
Sidi ChenDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. sidi.chen@yale.edu.ORCID http://orcid.org/0000-0002-3819-5005

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9M
(PQ4) Novel tools for in vivo study of genetic interactions in cancer progressionR01CA231112 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2022
$3.0M
High-throughput in vivo genetics for immunotherapy target discoveryDP2CA238295 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2018 to 2018
$2.5M
Advanced development of composite gene delivery and CAR engineering systemsR33CA281702 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2023 to 2025
$1.2M
Rapidly scalable platforms for direct in vivo screening of functional drivers in lethal cancersR33CA225498 · NCI · YALE UNIVERSITY · PI CHEN, SIDI · 2019 to 2021
$1.2M
Mechanosensation in tumorigenesis and metastasisF30CA250249 · NCI · YALE UNIVERSITY · PI CHOW, RYAN D · 2020 to 2022
$113k
NCI NIH HHS DP2 CA238295NCI NIH HHS F30 CA250249NCI NIH HHS R01 CA231112NCI NIH HHS R33 CA225498NCI NIH HHS R33 CA281702NIGMS NIH HHS T32 GM007205
6 · The paper itself

Abstract

The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR-Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (Cd274/Pdl1, Lgals9/Galectin9, Lgals3/Galectin3 and Cd47; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8

Indexed as

ImmunotherapyNeoplasmsAnimalsCell Line, TumorCRISPR-Cas SystemsDependovirusFemaleGene SilencingHumansMiceMice, Inbred C57BLTumor Microenvironment

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.