Peptide spiders are emerging as novel therapeutic interventions for nucleic acid delivery

Mahfoozur Rahman; Ankit Sahoo; Waleed H Almalki; Salem Salman Almujri; Abdulmalik Saleh Alfawaz Altamimi; Abdurrahman Alhamyani; Sohail Akhter

doi:10.1016/j.drudis.2024.104021

Peptide spiders are emerging as novel therapeutic interventions for nucleic acid delivery

Drug Discov Today. 2024 May 17;29(7):104021. doi: 10.1016/j.drudis.2024.104021. Online ahead of print.

Authors

Mahfoozur Rahman¹, Ankit Sahoo², Waleed H Almalki³, Salem Salman Almujri⁴, Abdulmalik Saleh Alfawaz Altamimi⁵, Abdurrahman Alhamyani⁶, Sohail Akhter⁷

Affiliations

¹ Department of Pharmaceutical Sciences, Shalom Institute of Health & Allied Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Allahabad 211007, Uttar Pradesh, India. Electronic address: mahfoozur.rahman@shiats.edu.in.
² College of Pharmacy, J.S. University, Shikohabad, Firozabad, Uttar Pradesh 283135, India.
³ Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.
⁴ Department of Pharmacology, College of Pharmacy, King Khalid University, Asir-Abha 61421, Saudi Arabia.
⁵ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia.
⁶ Pharmaceuticals Chemistry Department, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia.
⁷ Senior Principal Scientist, Global R&D, Pfizer, Sandwich, UK.

PMID: 38750928
DOI: 10.1016/j.drudis.2024.104021

Abstract

The FDA has approved many nucleic acid (NA)-based products. The presence of charges and biological barriers however affect stability and restrict widespread use. The electrostatic complexation of peptide with polyethylene glycol-nucleic acids (PEG-NAs) via nonreducible and reducible agents lead to three parts at one platform.. The reducible linkage made detachment of siRNA from PEG easy compared with a nonreducible linkage. A peptide spider produces a small hydrodynamic particle size, which can improve drug release and pharmacokinetics. Several examples of peptide spiders that enhance stability, protection and transfection efficiency are discussed. Moreover, this review also covers the challenges, future perspectives and unmet needs of peptide-PEG-NAs conjugates for NAs delivery.

Keywords: Cancer; Challenges; Unmet need; clinical progress; gene delivery; nucleic acid; peptides; peptide–PEG conjugates; polyethylene glycol, peptide-NAs.

Publication types

Review