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R&D: Low-Bias Manipulation of DNA Oligo Pool for Robust Storage

Combination of SDA and OPN can provide ideal amplification mechanism for low-bias copy of large oligo pool, which is of vital importance for successful data retrieval in DNA information storage.

ACS SyntheticBiology has published an article written by Yanmin Gao,School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P. R. China, and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, P. R. China, Xin Chen,Center for Applied Mathematics, Tianjin University, Tianjin 300350, P. R. China, Hongyan Qiao, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P. R. China, and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, P. R. China, Yonggang Ke, Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia 30322, USA, and Hao Qi., School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, P. R. China, and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, P. R. China.

Abstract: “In DNA data storage, the massive sequence complexity creates challenges in repeatable and efficient information readout. Here, our study clearly demonstrated that PCR created significant DNA amplification biases due to its inherent mechanism of inefficient priming, product-as-template, and error-spreading prone, which greatly hinder subsequent applications such as data retrieval in DNA-based storage. To mitigate the amplification bias, we recruited an isothermal DNA amplification by combining strand displacement amplification (SDA) with magnetic beads (MB) DNA immobilization for robust, repeated, and low-bias amplification of DNA oligo pool, comprising over 100 thousand oligos, in a primer-free and low-error-spreading fashion. Furthermore, we introduced oligo pool normalization (OPN), a cost-effective and scalable method for normalizing an oligo pool, by which oligo pools comprising from 256 to 1024 distinct oligos were simply modified with improved Gini-index. Therefore, we believe that the combination of SDA and OPN can provide an ideal amplification mechanism for a low-bias copy of a large oligo pool, which is of vital importance for successful data retrieval in DNA information storage.

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