Engineering cyclized biomolecules for advanced diagnostic and therapeutic applications

Biotechnol Adv. 2025 Nov:84:108694. doi: 10.1016/j.biotechadv.2025.108694. Epub 2025 Aug 22.

Abstract

Nucleic acids, peptides, and proteins demonstrate remarkable structural diversity and play essential roles in various biological processes. These biomolecules function as ligands, diagnostic agents, and therapeutic cargoes. However, their practical applications are often limited by inherent instability and inefficient delivery for targeted diagnosis and therapy. Cyclization has emerged as a promising solution, endowing these biomolecules with enhanced conformational rigidity, resistance to degradation, and a broader range of biological activities. Cyclic architectures not only enhance antitumor, anti-inflammatory, and anti-infective properties, but also eliminate the need for auxiliary carriers in some applications. This deliberate cyclization further enables precise control over binding affinity, stability, and membrane permeability. In this review, we cover diverse engineering methods for creating cyclized biomolecules and explore their applications in biosensing, targeted imaging, and delivery. Moving beyond naturally occurring forms, we highlight rationally engineered cyclized constructs that substantially expand their theranostic landscape in biology and biotechnology.

Keywords: Cyclization; Delivery; Diagnosis; Nucleic acid; Peptide; Protein; Stability; Therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Biosensing Techniques
  • Cyclization
  • Drug Delivery Systems
  • Humans
  • Nucleic Acids* / chemistry
  • Protein Engineering*
  • Proteins* / chemistry

Substances

  • Proteins
  • Nucleic Acids