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Targeted Delivery of Proteins into the Central Nervous System Mediated by Rabies Virus Glycoprotein-Derived Peptide

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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 t1/2 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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ACKNOWLEDGMENTS & DISCLOSURES

This work is supported by the grants from the Natural Science Foundation of China (31072098), the Doctoral Fund of Ministry of Education of China (20090182120017) and the Fundamental Research Funds for the Central Universities of China (XDGK2009C174).

We are grateful to Miss Lixin Xiang for pcDNA/Lac Z plasmid, to Dr. Ying Bin Yang for pVAX/Luc plasmid, and to Dr. Jian Ping Zhou for pGST-4T/BDNF plasmid.

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  1. School of Pharmaceutical Sciences, Southwest University, Tian Sheng Road, Beibei District, Chongqing, 400716, China

    Ailing Fu, Yilin Wang, Liping Zhan & Rumei Zhou

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  1. Ailing Fu
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  2. Yilin Wang
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  3. Liping Zhan
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Correspondence to Ailing Fu.

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Fu, A., Wang, Y., Zhan, L. et al. Targeted Delivery of Proteins into the Central Nervous System Mediated by Rabies Virus Glycoprotein-Derived Peptide. Pharm Res 29, 1562–1569 (2012). https://doi.org/10.1007/s11095-012-0667-y

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  • DOI: https://doi.org/10.1007/s11095-012-0667-y

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