The direct intracellular delivery of biologically active compounds, such as proteins or active peptide domains has been difficult to achieve primarily due to the bioavailability barrier of the plasma membrane. It effectively prevents the uptake of macromolecules by limiting their passive entry. The development of molecular techniques over the past several decades for the delivery of genes and proteins has provided tremendous advances in the understanding of cellular processes but has been of little benefit for the management of genetic disorders. The transfer of genetic material into eukaryotic cells either using viral vectors or by non-viral mechanisms (microinjection, electroporation, chemical transfection) remains problematic. Moreover, in vivo gene therapy approaches relying on adenoviral vectors are associated with significant difficulties relating to a lack of target specificity and toxicity which have contributed to poor performance in several clinical trials. The identification of a particular group of proteins with enhanced ability to cross the plasma membrane in a receptor-independent manner has led to the discovery of a class of protein domains with cell membrane penetrating properties. The fusion of these protein transduction domain peptides with heterologous proteins is sufficient to cause their rapid transduction into a variety of different cells in a rapid, concentration-dependent manner. It seems that this novel technique for protein and peptide delivery circumvents many problems associated with DNA and drug based methods. This technique may offer a unique procedure for the modulation of cell functions and the treatment of diseases.
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