Virus‐inspired and mimetic designs in non‐viral gene delivery

Abstract

Virus‐inspired mimics for nucleic acid transportation have attracted much attention in the past decade, especially the derivative microenvironment stimuli‐responsive designs. In the present mini‐review, the smart designs of gene carriers that overcome biological barriers and realize an efficient delivery are categorized with respect to the different “triggers” provided by tumor cells, including pH, redox potentials, ATP, enzymes and reactive oxygen species. Some dual/multi‐responsive gene vectors have also been introduced that show a more precise and efficient delivery in the complicated environment of human body. In addition, inspired by the special recognition mechanisms and components of viruses, improvements in the design of carriers relating to targeting/penetration properties, as well as chemical component evolution, are also addressed.

Optimizing pDNA Lipo-polyplexes: A Balancing Act between Stability and Cargo Release

“…Gene therapy is a potent field of modern, personalized medicine for tumor and genetic diseases, and its impact is growing continuously . However, there are still a lot of hurdles to deal with, especially in the case of synthetic therapeutic nucleic acid carriers. − Cellular internalization of nucleic acids across lipid membranes is hindered due to their big size and, in most cases, negative charge. Therefore, appropriate carrier systems are required for efficient delivery of nucleic acids, comprising extracellular stabilization and protection, efficient cellular uptake, and intracellular cargo release .…”

Histidine‐enhanced gene delivery systems: The state of the art

“…These genetic changes, mutations and interactions are not readily detectable in the short term; therefore, there are still safety concerns concerning gene therapy using viral vectors. Therefore, the discovery of efficient non‐viral vectors has been a hot topic in recent years because they do not show unwanted interactions with genetic material or lead to the development of harmful mutations 11–15 . Non‐viral vectors have often been designed based on biodegradable polymers, which can be optimized to form complexes with nucleic acids, can be stable in different environments and can escape from endosomes after cellular uptake 16–19 .…”

“…Therefore, the discovery of efficient non-viral vectors has been a hot topic in recent years because they do not show unwanted interactions with genetic material or lead to the development of harmful mutations. [11][12][13][14][15] Non-viral vectors have often been designed based on biodegradable polymers, which can be optimized to form complexes with nucleic acids, can be stable in different environments and can escape from endosomes after cellular uptake. [16][17][18][19] Additional factors, such as cytotoxicity, controlled release of nucleic acids and interactions with cells and tissues, all require physical and chemical optimization in the laboratory phase.…”

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

“…Therefore, non-viral synthetic delivery systems have been developed as alternative [ 14 ]. Such synthetic carriers can be virus-inspired and contain different domains to mimic the efficient, dynamic virus-based infection process [ 15 ].…”