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可降解玻璃态聚合物网络中可逆的核酸存储。

Reversible Nucleic Acid Storage in Deconstructable Glassy Polymer Networks.

机构信息

Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

Cache DNA, Inc., 733 Industrial Road, San Carlos, California 94070, United States.

出版信息

J Am Chem Soc. 2024 Jun 26;146(25):17066-17074. doi: 10.1021/jacs.4c01925. Epub 2024 Jun 12.

Abstract

The rapid decline in DNA sequencing costs has fueled the demand for nucleic acid collection to unravel genomic information, develop treatments for genetic diseases, and track emerging biological threats. Current approaches to maintaining these nucleic acid collections hinge on continuous electricity for maintaining low-temperature and intricate cold-chain logistics. Inspired by the millennia-long preservation of fossilized biological specimens in calcified minerals or glassy amber, we present Thermoset-REinforced Xeropreservation (T-REX): a method for storing DNA in deconstructable glassy polymer networks. Key to T-REX is the development of polyplexes for nucleic acid encapsulation, streamlining the transfer of DNA from aqueous to organic phases, replete with initiators, monomers, cross-linkers, and thionolactone-based cleavable comonomers required to form the polymer networks. This process successfully encapsulates DNA that spans different length scales, from tens of bases to gigabases, in a matter of hours compared to days with traditional silica-based encapsulation. Further, T-REX permits the extraction of DNA using comparatively benign reagents, unlike the hazardous hydrofluoric acid required for recovery from silica. T-REX provides a path toward low-cost, time-efficient, and long-term nucleic acid preservation for synthetic biology, genomics, and digital information storage, potentially overcoming traditional low-temperature storage challenges.

摘要

DNA 测序成本的迅速下降推动了人们对核酸收集的需求,以揭示基因组信息、开发治疗遗传疾病的方法,并追踪新出现的生物威胁。目前维持这些核酸库的方法依赖于持续的电力供应来维持低温和复杂的冷链物流。受化石生物标本在钙化矿物或玻璃质琥珀中经历数千年保存的启发,我们提出了热固性增强干保存(Thermoset-REinforced Xeropreservation,T-REX):一种将 DNA 存储在可解构玻璃状聚合物网络中的方法。T-REX 的关键是开发用于核酸封装的聚集体,简化了从水相到有机相的 DNA 转移,其中包含形成聚合物网络所需的引发剂、单体、交联剂和基于硫代内酰胺的可裂解共聚单体。与传统的基于二氧化硅的封装相比,该过程可在数小时内成功封装跨越不同长度尺度的 DNA,从数十个碱基到千兆碱基。此外,T-REX 允许使用相对良性的试剂提取 DNA,而不像从二氧化硅中回收所需的危险氢氟酸。T-REX 为合成生物学、基因组学和数字信息存储提供了一种低成本、高效、长期的核酸保存方法,可能克服了传统的低温存储挑战。

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