Cardiac Usage of Reducible Poly(oligo-D-arginine) As a Gene Carrier for Vascular Endothelial Growth Factor Expression

Abstract

Developments of non-viral carriers have headed toward reducing cytotoxicity, which results from the use of conventional gene carriers, and enhancing gene delivery efficiency. Cys-(d-R9)-Cys repeated reducible poly(oligo-D-arginine) (rPOA) is one of the most efficient non-viral carriers for gene therapy; however, while its efficiency has been verified in the lung and brain, it is necessary to confirm its activity in each organ or tissue since there are differences of gene carrier susceptibility to among tissue types. We therefore tested the compatibility of rPOA in cardiac tissue by in vitro or in vivo experiments and confirmed its high transfection efficiency and low cytotoxicity. Moreover, substantial regenerative effects were observed following transfection with rPOA/pVEGF expression vector complexes (79% decreased infarct size) compared to polyethyleneimine (PEI) (34% decreased infarct size) in a rat myocardial infarction (MI) model. These findings suggest that rPOA efficiently enables DNA transfection in cardiac tissue and can be used as a useful non-viral therapeutic gene carrier for gene therapy in ischemic heart disease.

Biopolymeric Materials Used as Nonviral Vectors: A Review

“…Table 2 presents the main factors evaluated in the articles about to the efficiency of gene transfection and bacterial transformation by different biopolymers and polysaccharides derivates: chitosan [19], dextran [20,21], quaternized cellulose [22] and quaternized chitosan [23]. Other types of substances were used as nonviral vectors such as: plasmid DNA nanostructures with ionic liquid [11], pegylated polyethyleneimine nanoparticles conjugated with folate and galactose [24], cationic liposomes modified with polyallylamine [25], biodegradable polylactic acid-polyethylene glycol-poly (L-lysine) copolymer [26], crotamine [27], poly (oligo-D-arginine) [28], poly (lactic acid-co-glycolic acid) scaffolds [29], polyethyleneimine/pDNA nanocomplexes with anionic hyaluronic acid [30], fourth generation cationic phosphorus (P4) containing dendrimers [31], and monosylated polyethyleneimine [32]. All the materials tested on these studies showed low cytotoxicity and enhanced significantly the efficiency (p < 0.05).…”

Peptide-Based Nanoassemblies in Gene Therapy and Diagnosis: Paving the Way for Clinical Application

“…Lesion size measured by computer-associated morphometry revealed a 30% decrease in the mean lesion area of the aortic sinus, for groups treated with peptiplexes, compared to the control groups ( Figure 10 D,E). Several other in vivo studies validated reducible poly(oligo-D-arginine) (rPOA)/pDNA complexes as an efficient non-viral gene carrier in the treatment of hypoxic–ischemic brain injury, spinal cord tumors, and in ischemic heart and lung diseases [ 140 , 141 , 142 , 143 ].…”

Advances in D-Amino Acids in Neurological Research

“…Other groups have also found that poly-arginine peptides are about to inhibit neuronal cell death by reducing stress-induced hyperpolarization of the mitochondria [ 63 , 138 , 139 , 140 , 141 ]. Additionally, poly-D-arginine peptides have been shown to be of use in gene therapy as non-viral carriers of genes [ 142 , 143 , 144 , 145 ]. This is due to their promotion of cell survival, allowing for introduction of a new gene while simultaneously preventing cellular stress [ 142 , 143 , 144 , 145 ].…”

“…Additionally, poly-D-arginine peptides have been shown to be of use in gene therapy as non-viral carriers of genes [ 142 , 143 , 144 , 145 ]. This is due to their promotion of cell survival, allowing for introduction of a new gene while simultaneously preventing cellular stress [ 142 , 143 , 144 , 145 ]. This shows that D-arginine’s neuroprotective effects make it a useful tool for decreasing infarct volume after stroke, ischemic or hypoxic damage to the brain.…”