一种通过操纵基因非编码区延缓细胞衰老的方法

By intervening in the selective polyadenylation (APA) pattern of the KIAA1549 gene using whole-genome CRISPRpas screening technology, the problem of the failure of existing technologies to effectively delay cell senescence was solved, and the improvement of cell senescence phenotype and proliferation capacity were achieved.

CN119464388BActive Publication Date: 2026-07-17FUDAN UNIVERSITY

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
FUDAN UNIVERSITY
Filing Date
2024-10-31
Publication Date
2026-07-17

AI Technical Summary

Technical Problem

Current technologies have not effectively utilized CRISPRpas to regulate cellular senescence, and methods to delay cellular senescence by manipulating non-coding regions of genes have not been reported.

Method used

Using whole-genome CRISPRpas screening technology, a gRNA library targeting the selective 3′UTR of a gene was designed and constructed. This library intervened in the selective polyadenylation (APA) pattern of the KIAA1549 gene, shortening the 3′UTR length and thus delaying cellular senescence.

Benefits of technology

It significantly improves cellular senescence phenotype, enhances cell proliferation, reduces the proportion of SA-β-gal positive cells, increases the proportion of MKI67 positive cells, downregulates CDKN1A expression, regulates LMNB1 and IL1A expression, and prevents carcinogenesis risk.

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Abstract

本发明公开了一种通过操纵基因非编码区延缓细胞衰老的方法;本发明通过全基因组CRISPRpas筛选分析发现重编程某些基因的选择性多聚腺苷酸化APA能够有效改善细胞衰老表型,从干预基因非编码区的角度为延缓细胞衰老的治疗提供新的手段。本发明利用CRISPRpas干预基因KIAA1549的选择性多聚腺苷酸化APA,使其维持和年轻时相当的3′UTR亚型比例,能够有效延缓细胞衰老表型。
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