EKC2023

DNA nanoengineering for efficient DNA-based data storage and high throughput proteomics

Aug 17, 2023, 5:15 PM

15m

Taurus 1

Life Science & Health [LH6] Disruptive Innovations in the Biomedical Space: Science, Technology and Commercialization

Speaker

Hansol Choi (Harvard Medical School)

Description

Synthetic DNA plays an essential role in many applications, from DNA structural nanotechnology and synthetic biology, to diagnostics and proteomics, serving as a programmable material that can enable Ångström-level positional control [1, 2]. However, to maximize the utility of DNA in these applications, additional engineering efforts are required, such as quality control or precise arrangement of the oligonucleotides (oligos). This presentation introduces two such DNA-based technologies that can increase efficiency in DNA-based data storage and throughput in proteomics.
Firstly, multiplex oligo library purification by synthesis and selection (MOPSS), a method that distinguishes error-free oligos from complex oligo libraries will be presented [3]. Despite advancements in oligo synthesis in terms of throughput and cost over the past decades, synthetic errors remain a challenge. The presence of synthetic errors reduces the efficiency of application. For example, when oligos are used to store digital information by converting binary information to quaternary DNA sequences, synthetic errors might lead to information loss or lower information density. To address this challenge, MOPSS measures oligo lengths by molecular dictation in a highly parallel manner to acquire full-length oligos without synthetic errors. Furthermore, millions of digital data-encoded oligo libraries are purified in one pot by repurposing a next generation sequencing (NGS) instrument. By increasing the quality of oligo libraries regardless of their sequences or complexity, MOPSS enhances not only the efficiency of DNA-based data storage, but also that of various biotechnological applications such as synthetic biology.
Additionally, a technology that can precisely arrange oligos on a solid substrate with high programmability will be presented. Patterning the surface with multiple oligos has been one of the major goals in DNA nanoengineering since it allows spatially resolved DNA-based analysis such as sequencing [4]. However, previous approaches lacked programmability or throughput. With the proposed technology, oligos are arranged at desired distances without the need for lithography instruments. The arranged oligos can be used as tethers for functional oligos, proteins, or cells to explore their biophysical properties with single-molecule resolution. The technology will facilitate high-resolution single-molecule measurements of proteins and will accelerate high-throughput proteomics research.

References

[1] Kosuri, Sriram, and George M. Church. "Large-scale de novo DNA synthesis: technologies and applications." Nature methods 11.5 (2014): 499-507.
[2] Choi, Yeongjae, et al. "A reconfigurable DNA accordion rack." Angewandte Chemie International Edition 57.11 (2018): 2811-2815.
[3] Choi, Hansol, et al. "Purification of multiplex oligonucleotide libraries by synthesis and selection." Nature Biotechnology 40.1 (2022): 47-53.
[4] Scheideler, Olivia J., et al. "Recapitulating complex biological signaling environments using a multiplexed, DNA-patterning approach." Science advances 6.12 (2020): eaay5696.