Characterization of a multifunctional PEG-based gene delivery system containing nuclear localization signals and endosomal escape peptides

Peptides as Promising Non-Viral Vectors for Gene Therapy

“…As an internalisation enhancer, tat 43-60 was displayed on the surfaces of phage particles to augment the delivery of plasmids encapsulated within the phages (Eguchi et al, 2001). In another study, tat 47-57 was used more as a NLS during the transfection of CHO cells (Moore et al, 2009). Unlike many other systems, the presence of serum augmented tatmediated transfection (Astriab-Fisher et al, 2000;Eguchi et al, 2001).…”

“…As a result, targeting signals on the carrier can become blocked or complexes can start to aggregate. Reducing or removing serum from the media during in vitro transfection can mitigate such effects and improve transfection (Moore et al, 2009;Moulton et al, 2004). However, this strategy fails during in vivo experiments where serum proteins are unavoidably present.…”

“…This suggests that the proton-sponge hypothesis can at best contribute, but cannot be the only cause of endosomal escape. Moreover, increased buffering and endosomal escaping properties do not always produce an accompanying increase in transfection (Akita et al, 2010;Moore et al, 2009). This implies that, while important, cytosolic access is not the only bottleneck of the transfection process.…”

“…The most commonly used sequence for SV40 is provided in Table 1. Other sequences include "glu-asp-pro-tyr" (Trentin et al, 2005) and "glu-pro-tyr-cys" (Moore et al, 2009) being added onto the C-terminus and an even longer form of SV40 has been described (Eguchi et al, 2001). INF 5 and INF 7 are examples of two commonly used fusogenic peptide and both are derived from the parent HA2 peptide (Plank et al, 1994).…”

The Pharmacology of Regenerative Medicine

“…Systems with reduced levels of toxicity and improved transgene expression are being developed through increased understanding of the role of chemical constituents of the delivery vehicle (Liu and Reineke, 2010). Peptidic sequences have been conjugated to various nonviral gene delivery systems to improve cellular uptake , subcellular transport (Kwon et al, 2008;Moseley et al, 2010), and nuclear localization (Jeon et al, 2007;Moore et al, 2009). Based on safety and toxicity profiles, it is conceivable that these approaches may supplant viral technologies for gene delivery (Li and Huang, 2007).…”