Published October 1, 2004
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Delivery of bioactive molecules into the cell: the Trojan horse approach
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In recent years, vast amounts of data on the mechanisms of neural deand
regeneration have accumulated. However, only in disproportionally
few cases has this led to efficient therapies for human patients. Part
of the problem is to deliver cell death-averting genes or gene products
across the blood– brain barrier (BBB) and cellular membranes. The
discovery of Antennapedia (Antp)-mediated transduction of heterologous
proteins into cells in 1992 and other ''Trojan horse peptides''
raised hopes that often-frustrating attempts to deliver proteins would
now be history. The demonstration that proteins fused to the Tat
protein transduction domain (PTD) are capable of crossing the BBB
may revolutionize molecular research and neurobiological therapy.
However, it was only recently that PTD-mediated delivery of proteins
with therapeutic potential has been achieved in models of neural
degeneration in nerve trauma and ischemia. Several groups have
published the first positive results using protein transduction domains
for the delivery of therapeutic proteins in relevant animal models of
human neurological disorders. Here, we give an extensive review of
peptide-mediated protein transduction from its early beginnings to new
advances, discuss their application, with particular focus on a critical
evaluation of the limitations of the method, as well as alternative
approaches. Besides applications in neurobiology, a large number of
reports using PTD in other systems are included as well. Because each
protein requires an individual purification scheme that yields sufficient
quantities of soluble, transducible material, the neurobiologist will
benefit from the experiences of other researchers in the growing field of
protein transduction.
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