Tools and techniques for the discovery of therapeutic aptamers: recent advances

Expert Opin Drug Discov. 2023 Jul-Dec;18(12):1393-1411. doi: 10.1080/17460441.2023.2264187. Epub 2023 Nov 1.

Abstract

Introduction: The pursuit of novel therapeutic agents for serious diseases such as cancer has been a global endeavor. Aptamers characteristic of high affinity, programmability, low immunogenicity, and rapid permeability hold great promise for the treatment of diseases. Yet obtaining the approval for therapeutic aptamers remains challenging. Consequently, researchers are increasingly devoted to exploring innovative strategies and technologies to advance the development of these therapeutic aptamers.

Areas covered: The authors provide a comprehensive summary of the recent progress of the SELEX (Systematic Evolution of Ligands by EXponential enrichment) technique, and how the integration of modern tools has facilitated the identification of therapeutic aptamers. Additionally, the engineering of aptamers to enhance their functional attributes, such as inhibiting and targeting, is discussed, demonstrating the potential to broaden their scope of utility.

Expert opinion: The grand potential of aptamers and the insufficient development of relevant drugs have spurred countless efforts for stimulating their discovery and application in the therapeutic field. While SELEX techniques have undergone significant developments with the aid of advanced analysis instruments and ingeniously updated aptameric engineering strategies, several challenges still impede their clinical translation. A key challenge lies in the insufficient understanding of binding conformation and susceptibility to degradation under physiological conditions. Despite the hurdles, our opinion is optimistic. With continued progress in overcoming these obstacles, the widespread utilization of aptamers for clinical therapy is envisioned to become a reality soon.

Keywords: SELEX technique; Therapeutic aptamers; aptamer engineering; protein degradation; receptor protein blockade; targeted therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aptamers, Nucleotide* / pharmacology
  • Humans
  • Ligands
  • Molecular Targeted Therapy
  • SELEX Aptamer Technique* / methods

Substances

  • Aptamers, Nucleotide
  • Ligands