Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Second generation CPPs with improved endosome release

Cell penetrating peptides (CPP) have been intensively studied as delivery vectors for various bio-molecules. However, their cellular internalisation mainly occurs through endocytosis and leads to sequestration within endocytic vesicles. It is now recognized, largely though our own studies, that escape from endosomes is the limiting factor for the efficient delivery of bio-molecules as peptides or nucleic acids. This is an important issue knowing the potential applications of these bio-molecules in bio-technomogy.

In keeping with this hypothesis, endosomolytic agents as chloroquine largely increase the nuclear delivery of oligonucleotide analogs (2OMe,PNA,PMO) cojugated to CPPs. Ongoing studies in collaboration with the groups of Dr.M.Gait in this consortium and Dr.H.Moulton (AVI Biopharma) are focusing on new CPPs which allow the nuclear delivery of conjugated oligonucleotides in the absence of endosomolytic agents. We have identified at least two such CPP derivatives, which are now the object of studies in terms of mechanism of cell internalisation and are subject to SAR studies.

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