Designed Peptide Assemblies for Efficient Gene Delivery

Abstract

The safe and efficient delivery of nucleic acids including DNA, mRNA, siRNA, and miRNA into targeted cells is critical for gene therapy. Currently, viral gene vectors are very popular, but they have potential toxicity and insecurity. Therefore, the development of nonviral vectors has attracted considerable research attention. Peptide assemblies are superior candidates for being used as gene vectors by having good biocompatibility, versatile molecular design, excellent assembly capacity, ease of modification, and stimuli responsivity. The de novo designed peptides not only can induce efficient condensation of nucleic acids into compacted nanoparticles and protect them from enzymatic digestion but also can effectively overcome biological barriers and improve gene delivery efficiency through targeted delivery, enhanced cellular uptake, improved endolysosomal escape, and nuclear importation. By having these merits, peptidic gene vectors are developing fast, showing outstanding advantages compared to liposome and polymer vectors. This Perspective focuses on peptidic gene delivery systems by emphasizing the molecular design strategies for meeting the criteria of gene condensation, protection from nuclease degradation, cellular uptake, endolysosomal escape, and so on. The new arising research area of peptide-based artificial viruses for gene and ribonucleoprotein delivery has also been reviewed. The challenges and future perspectives are put forward, aiming to provide a conclusive guide for the development of peptidic delivery systems to achieve efficient gene therapy.

Self-Assembly of Peptide–Lipid Nanoparticles for the Efficient Delivery of Nucleic Acids

“…Lysine-rich peptides could condense nucleic acids, histidine residue caused the “proton sponge effect”, resulting in the rupture of the endosomal membrane and released nucleic acids, and the hydrophobicity of leucine or phenylalanine residue achieved self-assembly and improved the interaction between peptides and cell membranes . Three peptides all had a good ability to bind nucleic acids, which could be proved by gel retardation assays (Figures A,B and S1). The existence of DOTAP would not change the condensation characteristics of the individual peptides (Figures C and S1).…”

InflammamiRs in focus: Delivery strategies and therapeutic approaches

“…Peptide‐based delivery vectors, including cell‐penetrating peptides (CPPs) and endosome‐disrupting peptides among others, 122 are versatile vectors that can facilitate the intracellular delivery and endosomal escape of miRNAs. Peptide vectors are promising since they are easily synthesized, modifiable, and biocompatible; however, they are usually not cell‐type‐specific and can be vulnerable to protease activity 123 …”

Blood–brain barrier disruption in dementia: Nano‐solutions as new treatment options

“…Additionally, peptide nanocomplexes can be formed that utilise a multi‐material approach to their design for a potential personalised treatment (Kwok et al, 2016; Ma & Cao, 2022; Peng et al, 2020). RALA, a peptide with repeat units of arginine‐alanine‐leucine‐alanine (R‐A‐L‐A) developed by McCarthy et al (2014), is an example of a peptide nanocomplex.…”