Polyplex: A Promising Gene Delivery System

Abstract


 
 
 In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.
 
 

Dendrimers as Non-Viral Vectors in Gene-Directed Enzyme Prodrug Therapy

“…There are several types of nVVs, commonly used in GDEPT, such as: polyplexes - short-lived electrostatic complexes that require an excess of polymer [ 69 ]; dendriplexes [ 70 ], lipoplexes [ 71 ], lipopolyplexes [ 72 ], lypodendriplexes [ 73 ], and micelles - dynamic amphiphilic polymers [ 74 ]. Nano-systems include: mesoporous nanoparticles [ 75 , 76 ], exosomes / microvesicles [ 77 ], organic / inorganic hybrids [ 78 , 79 ], nanofibres for from natural polymers [ 80 , 81 ], elecrospun nanofibers [ 82 ], niosomes / nioplexes [ 83 ], etc.…”

RNAi Crop Protection Advances

“…There is a large number of polymers for the manufacture of polyplexes, a limited list of the most used includes poly (ethyleneimine) (PEI) 69 , poly-L-Lysine (PLL), poly (amidoesters) (PAE) 70 , polyamidoamine (PAMAM), poly (2-dimethylaminoethyl methacrylate) (PDMAEMA) 71 , polyethylenglycol (PEG), Chitosan 72 , as well as copolymeric combinations such as phosphorylcholine-modified polyethyleneimine (PEI) PEGylated PEIbased, PEGylated poly (dimethylaminomethyl methacrylate) contai-ning folate, PEIgraftedα, β-poly (N-3-hydroxypropyl) -DL-aspartamide, galactose-modified trimethyl chitosan-cysteine-based, and others 73 . Theoretically, any positively charged polymer could form a polyplex, being of particular interest those biodegradable ones such as PEG, poly (glutamic acid) (PGA), poly (caprolactone) (PCL), poly (D, L-lactide-co-glycolide) (PLGA), poly (lactic acid) (PLA), N-(2-hydroxypropyl) -methacrylate copolymers (HPMA), polystyrene-maleic anhydride copolymer, and poly (amino acids) (PAAs) 73 .…”

“…Its main application is as a non-viral vector for DNA transfer in gene therapy including regenerative medicine 70 , AIDS, cancer, and hereditary disorders treatment 71 . It has also increased its use for transfection and editing of genomes in plants 76,77 , as well as for gene silencing systems mentioned above aimed to disease and pest control 23,38,44,78,79 .…”

RNAi Crop Protection Advances

“…There are a large number of polymers used for the manufacture of polyplexes, and a limited list of the most commonly used polymers includes poly(ethyleneimine) (PEI) 69 , poly-L-lysine (PLL), poly(amidoesters) (PAE) 70 , polyamidoamine (PAMAM), poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) 71 , polyethylene glycol (PEG), and chitosan 72 , as well as copolymeric combinations such as phosphorylcholine-modified polyethyleneimine (PEI) PEGylated PEI-based, PEGylated poly(dimethylaminomethyl methacrylate) containing folate, PEI-graftedα, β-poly(N-3-hydroxypropyl)-DL-aspartamide, galactose-modified trimethyl chitosan-cysteine-based, and others 73 . Theoretically, any positively charged polymer could form a polyplex, of particular interest being biodegradable polymers such as PEG, poly(glutamic acid) (PGA), poly(caprolactone) (PCL), poly(D,L-lactide-coglycolide) (PLGA), poly(lactic acid) (PLA), N-(2-hydroxypropyl)methacrylate copolymers (HPMA), polystyrene-maleic anhydride copolymer, and poly(amino acids) (PAAs) 73 .…”