Evidence map›Paper›PMID 34258164›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021

Programmable Unlocking Nano-Matryoshka-CRISPR Precisely Reverses Immunosuppression to Unleash Cascade Amplified Adaptive Immune Response.

Jin Yang, Zhike Li, Meiling Shen, Yan Wang, Li Wang, Jiamiao Li, Wen Yang, Jie Li, Haijun Li, Xinxin Wang and 2 more

Open access · goldAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
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

25 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
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  4. Frontiers in immunology · 2026
    Review
  5. Review
  6. Recent Advances in mRNA Delivery Systems for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
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  8. Article
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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

12 authors at 1 institution in 1 country.

Jin YangState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Zhike LiState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Meiling ShenState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Yan WangState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Li WangState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Jiamiao LiState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Wen YangState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Jie LiState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Haijun LiState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Xinxin WangState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Qinjie WuState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.
Changyang GongState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610041 P. R. China.ORCID 0000-0002-2913-0891
Sichuan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune checkpoint blockade (ICB) is an attractive option in cancer therapy, but its efficacy is still less than expected due to the transient and incomplete blocking and the low responsiveness. Herein, an unprecedented programmable unlocking nano-matryoshka-CRISPR system (PUN) targeting programmed cell death ligand 1 (PD-L1) and protein tyrosine phosphatase N2 (PTPN2) is fabricated for permanent and complete and highly responsive immunotherapy. While PUN is inert at normal physiological conditions, enzyme-abundant tumor microenvironment and preternatural intracellular oxidative stress sequentially trigger programmable unlocking of PUN to realize a nano-matryoshka-like release of CRISPR/Cas9. The successful nucleus localization of CRISPR/Cas9 ensures the highly efficient disruption of PD-L1 and PTPN2 to unleash cascade amplified adaptive immune response via revoking the immune checkpoint effect. PD-L1 downregulation in tumor cells not only disrupts PD-1/PD-L1 interaction to attenuate the immunosurveillance evasion but also spurs potent immune T cell responses to enhance adaptive immunity. Synchronously, inhibition of JAK/STAT pathway is relieved by deleting PTPN2, which promotes tumor susceptibility to CD8

Indexed as

Adaptive ImmunityAnimalsB7-H1 AntigenClustered Regularly Interspaced Short Palindromic RepeatsImmunosuppression TherapyMiceNanoparticlesProtein Tyrosine Phosphatase, Non-Receptor Type 2B7-H1 AntigenProtein Tyrosine Phosphatase, Non-Receptor Type 2Ptpn2 protein, mousecancer immunotherapycascade amplifiedCRISPR/Cas9nano‐matryoshkaprogrammable unlocking

Identifiers

PMID34258164
PMCPMC8261501
OpenAlexW3161204770

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.