Systemic circulation of poly(l-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy

Polyion complex micelles as vectors in gene therapy – pharmacokinetics and in vivo gene transfer

“…Thus, eventually, a fraction of linear DNA accumulates in time-dependent manner. This may be a reason for the apparent increase of linear DNA in the blood sample collected in the later time period, and is not necessarily inconsistent with observation by Ward et al 31 and Bronich et al 32 No small fragments of DNA were observed in any of the samples, suggesting that DNA in the PIC micelles is nuclease resistant in the blood. The results are in good agreement with the in vitro data previously described which showed resistance of PIC micelles to Dnase I.…”

Specific systemic nonviral gene delivery to human hepatocellular carcinoma xenografts in SCID mice

“…A similar DNA distribution within the liver was previously reported upon intravenous injection of transferrin-shielded DNA/PEI complexes 16 and DNA/poly-L-lysine complexes. 46 In conclusion, we have shown that intravenous injection of EP20P and EP40P DNA complexes allows for highly specific expression of a transgene in human HCC tumors in vivo without signs of acute toxicity. There are certainly a number of hurdles remaining to be overcome before the use of this strategy can be considered as a treatment option for patients with HCC.…”

Oligomers of the Arginine-rich Motif of the HIV-1 TAT Protein Are Capable of Transferring Plasmid DNA into Cells

“…Chemical properties of cationic polymers, such as the degree of polymerization, the type of cationic groups present in the polymer, or the amino acid composition of cationic oligopeptides influence the biophysical properties of their polyelectrolyte complexes with plasmid DNA. DNA binding affinity, surface charge, and particle size have pronounced effects on their efficacy in gene delivery and on biodistribution in vivo (13)(14)(15). Since compaction of DNA into stable microparticulate structures by oligopeptides suitable for gene transfer requires a minimum chain length of 6 -10 cationic amino acids (13), we synthesized the TAT peptide as oligomers.…”