Targeted delivery of proteins into the central nervous system mediated by rabies virus glycoprotein-derived peptide.
OBJECTIVE
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.
School of Pharmaceutical Sciences, Southwest University, Tian Sheng Road, Beibei District, Chongqing, 400716, China. Fuailing1008@hotmail.com
Ailing
A
Fu
Yilin
Y
Wang
Liping
L
Zhan
Rumei
R
Zhou
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002199:Capillary Permeability; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D006023:Glycoproteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007275:Injections, Intravenous; D008156:Luciferases / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011820:Rabies virus / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D014764:Viral Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001616:beta-Galactosidase / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D019208:Brain-Derived Neurotrophic Factor; D004337:Drug Carriers; D006023:Glycoproteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D008156:Luciferases; D001616:beta-Galactosidase