扩展DNA工程。
Scaling DNA engineering.
作者信息
Li Weiyi, Hung Po-Hsiang, Matsui Takeshi, Levy Sasha F, Sherlock Gavin
机构信息
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
BacStitch DNA Inc., Los Altos, CA, USA.
出版信息
Trends Biotechnol. 2025 May 28. doi: 10.1016/j.tibtech.2025.05.002.
DNA can be engineered to produce new biologics, gene therapies, and cellular therapies, and to reprogram organisms. Having the ability to engineer DNA at scale can accelerate the development of these applications. Existing technologies excel at short oligonucleotide synthesis by chemical or enzymatic methods (up to 2000 bp) and intermediate-size DNA assembly (up to 5-7 kb). Yet synthesizing sequence-validated longer DNA (>10 kb) and/or constructing highly complex combinatorial DNA libraries at scale remains a significant challenge, due largely to technical and cost barriers. Inspired by recent studies on an in vivo DNA processing platform for megabase-long DNA assembly and on high-throughput sequence verification, we discuss how these platforms may be used to achieve DNA engineering at scale.
DNA可以被设计用于生产新的生物制品、基因疗法和细胞疗法，以及对生物体进行重新编程。具备大规模设计DNA的能力可以加速这些应用的开发。现有技术在通过化学或酶促方法进行短寡核苷酸合成（长达2000 bp）和中等大小DNA组装（长达5 - 7 kb）方面表现出色。然而，大规模合成经过序列验证的更长DNA（>10 kb）和/或构建高度复杂的组合DNA文库仍然是一项重大挑战，这主要是由于技术和成本障碍。受近期关于用于兆碱基长DNA组装的体内DNA处理平台以及高通量序列验证研究的启发，我们讨论了如何利用这些平台实现大规模DNA工程。
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