From RNAi to single-cell CRISPR: Evolving functional screening in aging and cancer

Botao Fan; Aiwei Wu; Xue Pan; Hu Wang

doi:10.70401/acrt.2026.0031

From RNAi to single-cell CRISPR: Evolving functional screening in aging and cancer

Botao Fan

Aiwei Wu

Xue Pan

Hu Wang

Affiliation +

*Correspondence to: Hu Wang, Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, The Third People's Hospital of Deqing, Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. E-mail: wanghu19860315@163.com
Xue Pan, Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, The Third People's Hospital of Deqing, Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China. E-mail: panxue19950105@163.com

Ageing Cancer Res Treat. 2026;3:202621. 10.70401/acrt.2026.0031

Received: April 29, 2026Accepted: July 17, 2026Published: July 17, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Aging and cancer represent divergent fates of a common stress response. Senescence initially restrains malignancy through stable cell-cycle arrest and immune clearance, yet persistence of senescent cells and their secretory phenotype (SASP) paradoxically drives tumor progression, therapeutic resistance, and immune evasion via chronic inflammation and metabolic reprogramming. Functional genomic screening has evolved from bulk RNA interference to precision CRISPR modalities, including knockout, interference, activation, and base editing, and onward to single-cell and in vivo platforms. These technological advances have transformed our capacity to dissect cellular state transitions and network dependencies with unprecedented resolution. Here, we trace this technological evolution and synthesize its impact on aging and cancer research, with emphasis on chromatin regulation, metabolic rewiring, the SASP, nucleocytoplasmic transport, therapeutic response, and the tumor microenvironment. We emphasize that the current evidence derives predominantly from preclinical functional screens and computational predictions. We propose shifting from gene-centric discovery toward context-dependent network analysis. Integrating precise editing, in vivo screening, single-cell multi-omics, and emerging AI-assisted design may provide information and a design basis for future combined strategies that simultaneously target vulnerabilities in senescent cells and malignant populations.

Keywords

CRISPR screening, senescence, cancer, functional genomics

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Fan B, Wu A, Pan X, Wang H. From RNAi to single-cell CRISPR: Evolving functional screening in aging and cancer. Ageing Cancer Res Treat. 2026;3:202621. https://doi.org/10.70401/acrt.2026.0031

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Ageing and Cancer Research & Treatment

From RNAi to single-cell CRISPR: Evolving functional screening in aging and cancer

Botao Fan

Aiwei Wu

Xue Pan

Hu Wang

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From RNAi to single-cell CRISPR: Evolving functional screening in aging and cancer

Botao Fan

Aiwei Wu

Xue Pan

Hu Wang

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