Gene delivery to brain cells with apoprotein E derived peptide conjugated to polylysine (apoEdp-PLL).
A promising strategy to carry genetic material to brain cells either in vitro or in vivo is using the LDL receptor (LDLr) on blood-brain barrier. LDLr naturally help to low density lipoproteins (LDL(S)) transporting across the BBB by endocytosis. Here we present the idea of using the LDLr-mediated pathway for transporting genetic material to brain cells. A tandem dimer Sequence of apoprotein-E (apoE) (141-150) conjugated to polylysine sequence was used as a novel DNA Delivery vector for transfecting of brain cells either in vitro or in vivo. DNA condensation occurs with this vector because electrostatic interaction between DNA and polylysine. The vector favors to protection of DNA from enzymatic degradation and also helps to DNA carrying in blood stream to reach BBB and transport it to brain cells and eventually help DNA expression in target cells. These results suggest a novel gene delivery vector for gene therapy of brain disease.
Mousazadeh
Mohammad
M
Department of Clinical Biochemistry, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran. m_mosazadeh@yahoo.com
Palizban
Abbasali
A
Salehi
Rasool
R
Salehi
Mansoor
M
D000818:Animals; D001057:Apolipoproteins E / Q000737:chemistry* / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011107:Polylysine / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D001057:Apolipoproteins E; D010446:Peptide Fragments; D011973:Receptors, LDL; D011107:Polylysine; D004247:DNA; D001616:beta-Galactosidase