The role of the multifunctional antimicrobial peptide melittin in gene delivery

Bilal Ahamad Paray; Aqeel Ahmad; Javed Masood Khan; Faisal Taufiq; Aslam Pathan; Ajamaluddin Malik; Mohammad Z Ahmed

doi:10.1016/j.drudis.2021.01.004

The role of the multifunctional antimicrobial peptide melittin in gene delivery

Drug Discov Today. 2021 Apr;26(4):1053-1059. doi: 10.1016/j.drudis.2021.01.004. Epub 2021 Jan 12.

Authors

Bilal Ahamad Paray¹, Aqeel Ahmad², Javed Masood Khan³, Faisal Taufiq⁴, Aslam Pathan⁵, Ajamaluddin Malik⁶, Mohammad Z Ahmed⁷

Affiliations

¹ Department of Zoology, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Medical Biochemistry, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia. Electronic address: aqeelbiochem@gmail.com.
³ Department of Food Science and Nutrition, Faculty of Food and Agricultural Sciences, King Saud University 2460, Riyadh 11451, Saudi Arabia.
⁴ Department of Medical Anatomy, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia.
⁵ Department of Pharmacology, College of Medicine, Shaqra University, Shaqra 11961, Saudi Arabia.
⁶ Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
⁷ Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

PMID: 33450177
DOI: 10.1016/j.drudis.2021.01.004

Abstract

Melittin is vital for the endosomal escape of nanoparticles, but its excessive cytotoxicity in mammalian cells limits its value as a potential therapeutic agent. Several novel analogs of melittin have been optimized and characterized to establish a non-toxic melittin-based gene delivery system, in which the sequences of the melittin peptides were altered to reduce their cytotoxic activity. This review focusses on the involvement of melittin in nanoparticle endosomal escape and on the construction of melittin conjugates to boost gene delivery. Endosomal escape mechanisms for melittin, as well as the development of melittin as a therapeutic agent and its potential applications in nanomedicine, are discussed.

Publication types

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

MeSH terms

Antimicrobial Peptides / pharmacology
Endosomes / physiology
Gene Transfer Techniques*
Genetic Therapy* / methods
Genetic Therapy* / trends
Humans
Melitten* / analogs & derivatives
Melitten* / pharmacology
Nanoparticles / therapeutic use*

Substances

Antimicrobial Peptides
Melitten