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Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery. | LitMetric

Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery.

J Control Release

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; School of Chemical Sciences, Dublin City University, Dublin 9, Ireland. Electronic address:

Published: February 2021

AI Article Synopsis

  • - The study focuses on creating a non-viral gene delivery system that can safely transport functional nucleic acids to the right spot within cells, tackling challenges like toxicity, immune response, and various cellular barriers.
  • - A new peptide, called CHAT, was designed using specific amino acids to improve the delivery efficiency of DNA into cells, including features that enhance cell uptake and ensure stability.
  • - Among six peptides tested, CHAT proved successful in delivering DNA without harming cells, successfully entering cancer cell lines and demonstrating gene expression in live models, positioning it as a promising option for nucleic acid therapies.

Article Abstract

The design of a non-viral gene delivery system that can release a functional nucleic acid at the intracellular destination site is an exciting but also challenging proposition. The ideal gene delivery vector must be non-toxic, non-immunogenic, overcome extra- and intra-cellular barriers, protect the nucleic acid cargo from degradation with stability over a range of temperatures. A new 15 amino acid linear peptide termed CHAT was designed in this study with the goal of delivering DNA with high efficiency into cells in vitro and tissues in vivo. Rational design involved incorporation of key amino acids including arginine for nucleic acid complexation and cellular uptake, tryptophan to enhance hydrophobic interaction with cell membranes, histidine to facilitate endosomal escape and cysteine for stability and controlled cargo release. Six linear peptides were synthesised with strategic sequences and amino acid substitutions. Data demonstrated that all six peptides complexed pDNA to produce cationic nanoparticles less than 200 nm in diameter, but not all peptides resulted in successful transfection; indicating the influence of peptide design for endosomal escape. Peptide 4, now termed CHAT, was non-cytotoxic, traversed the plasma membrane of breast and prostate cancer cell lines, and elicited reporter-gene expression following intra-tumoural and intravenous delivery in vivo. CHAT presents an exciting new peptide for the delivery of nucleic acid therapeutics.

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Source
http://dx.doi.org/10.1016/j.jconrel.2020.11.037DOI Listing

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