Targeted delivery of proteins into the central nervous system mediated by rabies virus glycoprotein-derived Peptide.

Authors:
Address: School of Pharmaceutical Sciences, Southwest University, Tian Sheng Road, Beibei District, Chongqing, 400716, China, Fuailing1008@hotmail.com.
Journal:

Publication:

abstract

PURPOSE:

delivery of therapeutic proteins across the blood-brain barrier (BBB) is severely limited by their size and biochemical properties. Here we showed that a 39-amino acid Peptide derived from the rabies virus glycoprotein (RDP) was exploited as an efficient protein carrier for brain-targeting delivery.

METHODS:

Three proteins with different molecular weight and pI, β-galactosidase (β-Gal), luciferase (Luc) and brain-derived neurotrophic factor (BDNF), were fused to RDP and intravenously injected into the mice respectively. The slices of different tissues with X-Gal staining were used to examine whether RDP could deliver β-Gal Targeted into the CNS. The time-course relationship of RDP-Luc was studied to confirm the transport efficiency of RDP. The neuroprotective function of RDP-BDNF was examined in mouse experimental stroke to explore the pharmacological effect of RDP fusion protein.

RESULTS:

The results showed that the fusion proteins rapidly and specific entered the nerve cells in 15 min, and the t(1/2) was about 1 hr. Furthermore, RDP-BDNF fusion protein showed the neuroprotective properties in mouse experimental stroke including reduction of stroke volume and neural deficit.

CONCLUSIONS:

RDP provides an effective approach for the targeted delivery of biological active proteins into the central nervous system.

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