In vivo protein transduction to the CNS

Neuroscience
L T LoftusY Matsuoka

Abstract

Proteins and peptides are useful research and therapeutic tools, however applications are limited because delivery to the desired location is not easily achievable. There are two hurdles in protein/peptide delivery to the brain: the blood-brain barrier and intracellular penetration. Penetration to both brain and the intracellular space can be achieved by adjusting hydrophilicity, and small molecule pharmacological agents have been successfully developed using this approach. But with proteins and peptides, it is difficult to modify the hydrophilicity without influencing biological functions. Trans-acting factor protein from the human immunodeficiency virus contains a highly conserved cationic peptide sequence necessary for transduction across the cell membrane. While trans-acting factor peptide has been used for in vitro protein transduction, its in vivo application is very limited because it is rapidly degraded by proteolysis. Polyethylenimine is a chemically synthesized small molecule cationization agent; the charge density is greater than a peptide-based cationic cluster such as trans-acting factor, and it is resistant to proteolysis in vivo. We first tested intracellular protein transduction following direct brain injection ...Continue Reading

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Citations

Sep 11, 2008·Current Treatment Options in Neurology·Teodor T PostolacheLeonardo H Tonelli
Jun 28, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Leonardo H TonelliTeodor T Postolache
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Mar 31, 2017·EMBO Molecular Medicine·Yu-Sung ChengPang-Hsien Tu

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