Cell penetrating peptides: overview and applications to the delivery of oligonucleotides |
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Authors: | F Said Hassane A F Saleh R Abes M J Gait Bernard Lebleu |
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Institution: | 1. UMR 5235 CNRS, Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, 34095, Montpellier Cedex 5, France 2. Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge, CB2 0QH, UK
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Abstract: | Crossing biological barriers represents a major limitation for clinical applications of biomolecules such as nucleic acids,
peptides or proteins. Cell penetrating peptides (CPP), also named protein transduction domains, comprise short and usually
basic amino acids-rich peptides originating from proteins able to cross biological barriers, such as the viral Tat protein,
or are rationally designed. They have emerged as a new class of non-viral vectors allowing the delivery of various biomolecules
across biological barriers from low molecular weight drugs to nanosized particles. Encouraging data with CPP-conjugated oligonucleotides
have been obtained both in vitro and in vivo in animal models of diseases such as Duchenne muscular dystrophy. Whether CPP-cargo
conjugates enter cells by direct translocation across the plasma membrane or by endocytosis remains controversial. In many
instances, however, endosomal escape appears as a major limitation of this new delivery strategy. |
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