Recent Developments in Peptide-Based Nucleic Acid Delivery

Abstract

Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cellpenetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisenseoligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.

Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines

“…= 52.8 kDa vs. 2.1 or 2.8 kDa for TP10 and TP molecules, respectively) or small siRNA molecule which decreases mRNA ratio of SASH1 gene. Our investigation of TP and TP10 penetration into CRC cell lines may contribute to the results of other studies on CPP attached to peptides [23], short interfering RNA (siRNA) and DNA oligonucleotides [24] as well as peptide nucleic acid (PNA) oligomers [25].…”

“…Large protein delivery usually occurs by the way of endocytosis [25,48]. CPP/cargo complexes reside then in endosomal vesicles and only a minor portion of them is able to escape these compartments, which www.fhc.viamedica.pl decreases enormously the bioavailability of the transported substances [49].…”

Mutational Mapping of UL130 of Human Cytomegalovirus Defines Peptide Motifs within the C-Terminal Third as Essential for Endothelial Cell Infection

“…Thus, we hypothesized that the pentapeptide motif PNLIV in pUL130 might be involved in mediating endocytic uptake of HCMV in ECs, and if so, deletion of this motif should result in a nonendotheliotropic virus. A number of CPPs that are thought to be taken up by endocytosis have now been described, including VPMLK, PMLKE, VPTLK, KLPVM, and others (32). These CPPs all bear some similarity, but the exact amino acid sequence seems to be irrelevant.…”

Biomateriais para formulações de base nanotecnológica visando terapia gênica ocular

“…102 Uma alta densidade de aminoácidos básicos como lisina ou arginina (como é o caso da protamina) favorece o transporte até o núcleo celular através do complexo de poros nuclear. 104,105 Polietilenimina Polietilenimina (PEI) é um polímero linear ou ramificado, considerado um padrão-ouro de sistemas não virais para transfecção in vitro. 106,107 Inúmeros fatores estão relacionados à eficiência da PEI, como célula-alvo, peso molecular, ramificações, razão N/P entre os grupos amina da polietilenimina (N) e os grupos fosfato do ácido nucleico (P), e tamanho do complexo.…”