title: Magnetically enhanced adeno-associated viral vector delivery for human neural stem cell infection.
abstract: Gene therapy technology is a powerful tool to elucidate the molecular cues that precisely regulate stem cell fates, but developing safe vehicles or mechanisms that are capable of delivering genes to stem cells with high efficiency remains a challenge. In this study, we developed a magnetically guided adeno-associated virus (AAV) delivery system for gene delivery to human neural stem cells (hNSCs). Magnetically guided AAV delivery resulted in rapid accumulation of vectors on target cells followed by forced penetration of the vectors across the plasma membrane, ultimately leading to fast and efficient cellular transduction. To combine AAV vectors with the magnetically guided delivery, AAV was genetically modified to display hexa-histidine (6xHis) on the physically exposed loop of the AAV2 capsid (6xHis AAV), which interacted with nickel ions chelated on NTA-biotin conjugated to streptavidin-coated superparamagnetic iron oxide nanoparticles (NiStNPs). NiStNP-mediated 6xHis AAV delivery under magnetic fields led to significantly enhanced cellular transduction in a non-permissive cell type (i.e., hNSCs). In addition, this delivery method reduced the viral exposure times required to induce a high level of transduction by as much as to 2-10 min of hNSC infection, thus demonstrating the great potential of magnetically guided AAV delivery for numerous gene therapy and stem cell applications.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Eunmi
authors.initials: E
authors.lastname: Kim
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Oh
authors.forename: Ik-Sung
authors.initials: IS
authors.lastname: Ahn
authors.forename: Kook In
authors.initials: KI
authors.lastname: Park
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Jang
mesh_terms: D002460:Cell Line; D000229:Dependovirus / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D008280:Magnetics; D058953:Neural Stem Cells / Q000821:virology*