Gene Delivery Using Lipoplexes and Polyplexes: Principles, Limitations and Solutions

Peptides as key components in the design ofnon‐viralvectors for gene delivery

“…[5] All of these physical and biological barriers pose a significant engineering problem, and many vectors have been created in an attempt to bring clinical gene therapy into reality. Efforts are underway to develop vehicles composed from modified viruses, [2,6] polymers, [7,8] lipids, [8][9][10] cell penetrating peptides, [11,12] and other nano-assemblies. [13][14][15] Virus based vectors can package nucleic acids and facilitate integration into the genome of the transfected cell resulting in long term, stable expression.…”

“…[16] Polymers have been explored since they offer the ability to create higher order structures based on the properties of tunable monomers, however they also suffer from the potential for high immunogenicity, as well as complicated synthetic reaction schemes that are needed to create homogenous particles. [8] Cationic lipids are viewed as a safer alternative to polymers, but recent evidence has shown that these vectors can also provoke a harmful immune response at therapeutically relevant doses. [8,17] Cell penetrating peptides (CPP) are a subset of peptides that can condense nucleic acids through electrostatic interactions and have been investigated as non-viral gene carriers since the 1980's.…”

“…[8] Cationic lipids are viewed as a safer alternative to polymers, but recent evidence has shown that these vectors can also provoke a harmful immune response at therapeutically relevant doses. [8,17] Cell penetrating peptides (CPP) are a subset of peptides that can condense nucleic acids through electrostatic interactions and have been investigated as non-viral gene carriers since the 1980's. [36] CPPs are short chains of amino acids that assemble to form unique structures with distinct chemical properties.…”

“…[12,31,38,39] The sequences of CPPs allow them to cross the cell membrane, but challenges such as serum stability and endosomal escape present hurdles to successful gene delivery. [8] The use of polyethelene glycol [40] and groups capable of disrupting the endosome to release intact cargo [33] are being explored to address these shortcomings, but more work must be done before peptide-based gene delivery vehicles reach high enough levels of efficacy to become clinically relevant.…”

“…[ 8 ] Cationic lipids are viewed as a safer alternative to polymers, but recent evidence has shown that these vectors can also provoke a harmful immune response at therapeutically relevant doses. [ 8,17 ]…”