Strength of conjugate binding to plasmid DNA affects degradation rate and expression level in vivo

Suppression of tumor metastasis by NK4 plasmid DNA released from cationized gelatin

“…Some researchers indicate that polyionical complexation prevents the plasmid DNA from enzymatic degradation by DNase attack. [35][36][37] In this study, the gene expression of NK4 induced by the cationized gelatin microspheres incorporating NK4 plasmid DNA disappeared approximately 28 days after injection (Figure 6a). At the same time, the carrier microspheres were completely degraded in vivo and the remaining amount of NK4 plasmid DNA was almost zero (Figure 1).…”

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

“…Ogris et al 12 reported that PEGylated DNA transferring-PEI complexes have reduced interaction with blood components and extended circulation in blood. On the other hand, Mullen et al 34 reported that circulation time of PEGylated polyplex is shorter than that of polyplex. The polyplex with PL-PEG or PL-PEG-C 12 reported by Mullen et al 34 are more nuclease-sensitive than that without PEG, suggesting that the structure of their polyplex may be different from that of the PIC micelles in the present report.…”

“…On the other hand, Mullen et al 34 reported that circulation time of PEGylated polyplex is shorter than that of polyplex. The polyplex with PL-PEG or PL-PEG-C 12 reported by Mullen et al 34 are more nuclease-sensitive than that without PEG, suggesting that the structure of their polyplex may be different from that of the PIC micelles in the present report. Note that susceptibility to nuclease attack was appreciably decreased for DNA entrapped into our PIC micelles made from block copolymer.…”

The Mechanical Agitation Method of Gene Transfer for Ex-Vivo Gene Therapy

“…An exogenous gene in the lipoplexes would not have a chance to be released into the cytoplasm for gene expression if the endosomes are stable. Therefore, helper lipids are added to form lipoplexes to facilitate the endosomal escape of the exogenous gene (Herringson et al, 2009a(Herringson et al, , 2009bSavva et al, 2005 (Segura & Shea, 2001), cationic peptides consisting of poly-L-Lysine (D'Haeze et al, 2007;Mullen et al, 2000;Niidome et al, 1997), or other types of cationic proteins (De Lima et al, 1999;Jean et al, 2009;Lam et al, 2004;Lee et al, 2003;Oliveira et al, 2009;Vighi et al, 2007). These approaches produce DNA carrying complexes that are more stable.…”