A genetically encoded device for transcriptome storage in mammalian cells

• 成果类型: Article
• 署名作者: Chao, Yu-Kai; Wu, Michelle; Gong, Qiyu; Chen, Fei
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Harvard University; Harvard University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adz9353
• 发表日期: 2026-03-26
• 页码: eadz9353
• 关键词: rna-seq; cancer-cells; lung-cancer; VAULT; platform; particle

摘要

Understanding how cells make decisions over time requires the ability to link past molecular states to future phenotypic outcomes. We present TimeVault, a genetically encoded system that records and stores transcriptomes within living mammalian cells for future readout. TimeVault leverages engineered vault particles that capture messenger RNA through polyadenosine [poly (A)]-binding protein. We demonstrate that the transcriptome stored by TimeVaults is stable in living cells for more than 7 days. TimeVault enables high-fidelity transcriptome-wide recording with minimal cellular perturbation, capturing transient stress responses and revealing gene expression changes underlying drug-na & iuml;ve persister states in lung cancer cells that evade epidermal growth factor receptor (EGFR) inhibition. By linking past and present cellular states, TimeVault provides a powerful tool for decoding how cells respond to stress, make fate decisions, and resist therapy.