4.8 Article

Bioorthogonal information storage in L-DNA with a high-fidelity mirror-image Pfu DNA polymerase

期刊

NATURE BIOTECHNOLOGY
卷 39, 期 12, 页码 1548-+

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NATURE PORTFOLIO
DOI: 10.1038/s41587-021-00969-6

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资金

  1. National Natural Science Foundation of China [21925702, 32050178, 21750005]
  2. Tsinghua-Peking Center for Life Sciences
  3. Tencent Foundation
  4. Beijing Advanced Innovation Center for Structural Biology
  5. Beijing Frontier Research Center for Biological Structure

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Researchers have developed a mirror-image DNA that can store genetic information and is resistant to biodegradation, as well as synthesized a high-fidelity mirror-image DNA polymerase. They used this polymerase to encode an article about a mirror-image world in mirror-image DNA, and achieved chiral steganography. The study also showed that mirror-image DNA can be stored in water for longer periods of time, potentially advancing the development of mirror-image biology systems.
Natural DNA is exquisitely evolved to store genetic information. The chirally inverted L-DNA, possessing the same informational capacity but resistant to biodegradation, may serve as a robust, bioorthogonal information repository. Here we chemically synthesize a 90-kDa high-fidelity mirror-image Pfu DNA polymerase that enables accurate assembly of a kilobase-sized mirror-image gene. We use the polymerase to encode in L-DNA an 1860 paragraph by Louis Pasteur that first proposed a mirror-image world of biology. We realize chiral steganography by embedding a chimeric D-DNA/L-DNA key molecule in a D-DNA storage library, which conveys a false or secret message depending on the chirality of reading. Furthermore, we show that a trace amount of an L-DNA barcode preserved in water from a local pond remains amplifiable and sequenceable for 1 year, whereas a D-DNA barcode under the same conditions could not be amplified after 1 day. These next-generation mirror-image molecular tools may transform the development of advanced mirror-image biology systems and pave the way for the realization of the mirror-image central dogma and exploration of their applications.

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