RNA and Single-Stranded DNA Phages: Unveiling the Promise from the Underexplored World of Viruses

Int J Mol Sci. 2023 Dec 1;24(23):17029. doi: 10.3390/ijms242317029.

Abstract

RNA and single-stranded DNA (ssDNA) phages make up an understudied subset of bacteriophages that have been rapidly expanding in the last decade thanks to advancements in metaviromics. Since their discovery, applications of genetic engineering to ssDNA and RNA phages have revealed their immense potential for diverse applications in healthcare and biotechnology. In this review, we explore the past and present applications of this underexplored group of phages, particularly their current usage as therapeutic agents against multidrug-resistant bacteria. We also discuss engineering techniques such as recombinant expression, CRISPR/Cas-based genome editing, and synthetic rebooting of phage-like particles for their role in tailoring phages for disease treatment, imaging, biomaterial development, and delivery systems. Recent breakthroughs in RNA phage engineering techniques are especially highlighted. We conclude with a perspective on challenges and future prospects, emphasizing the untapped diversity of ssDNA and RNA phages and their potential to revolutionize biotechnology and medicine.

Keywords: CRISPR/Cas-based genome editing; RNA phages; genetic engineering; metaviromics; phage therapy; phage-based applications; ssDNA phages; synthetic rebooting.

Publication types

  • Review

MeSH terms

  • Bacteriophages* / genetics
  • CRISPR-Cas Systems
  • DNA, Single-Stranded / genetics
  • Gene Editing / methods
  • Genetic Engineering / methods
  • RNA
  • RNA Phages*

Substances

  • DNA, Single-Stranded
  • RNA

Grants and funding

This work was supported by the Takeda Science Foundation (to H.M.N.), the JSPS KAKENHI (Grant No. 22K19386 to S.W.), the Japan Agency for Medical Research and Development (Grant No. JP21fk0108497 to S.W., JP21ae0121045, JP22ae0121045, JP23ae0121045, JP21gm1610002, JP22gm1610002, JP23gm1610002, and JP22fk0108134 to L.C.), and Cabinet Office, Government of Japan (Grant No. JPJ009237 to L.C.).