Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein

TY - JOUR

T1 - Evolution of a virus-like architecture and packaging mechanism in a repurposed bacterial protein

AU - Tetter, Stephan

AU - Terasaka, Naohiro

AU - Steinauer, Angela

AU - Clark, Sam

AU - Scott, Andrew J.P.

AU - Patel, Nikesh

AU - Leibundgut, Marc

AU - Wroblewski, Emma

AU - Ban, Nenad

AU - Stockley, Peter G.

AU - Twarock, Reidun

AU - Hilvert, Donald

AU - Bingham, Richard John

N1 - © 2021 American Association for the Advancement of Science. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2021/6/11

Y1 - 2021/6/11

N2 - Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications.

AB - Viruses are ubiquitous pathogens of global impact. Prompted by the hypothesis that their earliest progenitors recruited host proteins for virion formation, we have used stringent laboratory evolution to convert a bacterial enzyme that lacks affinity for nucleic acids into an artificial nucleocapsid that efficiently packages and protects multiple copies of its own encoding messenger RNA. Revealing remarkable convergence on the molecular hallmarks of natural viruses, the accompanying changes reorganized the protein building blocks into an interlaced 240-subunit icosahedral capsid that is impermeable to nucleases, and emergence of a robust RNA stem-loop packaging cassette ensured high encapsidation yields and specificity. In addition to evincing a plausible evolutionary pathway for primordial viruses, these findings highlight practical strategies for developing nonviral carriers for diverse vaccine and delivery applications.

UR - http://www.scopus.com/inward/record.url?scp=85107811411&partnerID=8YFLogxK

U2 - 10.1126/science.abg2822

DO - 10.1126/science.abg2822

M3 - Article

C2 - 34112695

AN - SCOPUS:85107811411

SN - 0036-8075

VL - 372

SP - 1220

EP - 1224

JO - Science

JF - Science

IS - 6547

ER -