title: Recombinant single-chain antibody with the Trojan peptide penetratin positioned in the linker region enables cargo transfer across the blood-brain barrier.
abstract: Delivery of therapeutic proteins into tissues and across the blood-brain barrier (BBB) is limited by the size and biochemical properties of the proteins. Efficient delivery across BBB is generally restricted to small, highly lipophilic molecules. However, in the last decades, several peptides that can pass cell membranes have been identified. It has been shown that these peptides are also capable of delivering large hydrophilic cargoes into cells and are therefore a powerful biological tool for transporting drugs across cell membranes and even into the brain. We designed and prepared a single-chain antibody fragment (scFvs), specific for the pathological form of the prion protein (PrP(Sc)), where a cell-penetrating peptide (CPP) was used as a linker between the two variable domains of the scFv. The intravenously administered recombinant scFv-CPP was successfully targeted to and delivered into mouse brain cells. Our single-chain antibody fragments are of special interest in view of possible therapeutic reagents design not only for prion diseases but also for other neurodegenerative diseases.
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Nives
authors.initials: N
authors.lastname: Skrlj
authors.forename: Gorazd
authors.initials: G
authors.lastname: Drevenšek
authors.forename: Samo
authors.initials: S
authors.lastname: Hudoklin
authors.forename: Rok
authors.initials: R
authors.lastname: Romih
authors.forename: Vladka
authors.initials: V
authors.lastname: Curin Šerbec
authors.forename: Marko
authors.initials: M
authors.lastname: Dolinar
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D018621:PrPC Proteins; D057127:Single-Chain Antibodies