PMID- 26472457 OWN - NLM STAT- MEDLINE DCOM- 20160419 LR - 20181113 IS - 1940-6029 (Electronic) IS - 1064-3745 (Print) IS - 1064-3745 (Linking) VI - 1364 DP - 2016 TI - Intravascular AAV9 Administration for Delivering RNA Silencing Constructs to the CNS and Periphery. PG - 261-75 LID - 10.1007/978-1-4939-3112-5_21 [doi] AB - Viral vector delivery of RNA silencing constructs, when administered into vasculature, typically results in poor central nervous system (CNS) transduction due to the inability of the vector to cross the blood-brain barrier (BBB). However, adeno-associated virus serotype 9 (AAV9) has the ability to cross the BBB and robustly transduce brain parenchyma and peripheral tissues at biologically meaningful levels when injected intravenously. Recent work by our lab has shown that this method can be used to deliver RNA silencing constructs, resulting in significant reductions in gene expression in multiple brain regions and in peripheral tissues. Here, we outline a method for delivery of AAV9 vectors expressing RNA interference (RNAi) constructs that lead to robust simultaneous transduction of mouse peripheral tissues and the CNS following a single injection into the jugular vein. Additionally, we outline methods for necropsy and immunofluorescence to detect AAV9 transduction patterns in the rodent CNS following a vascular delivery. FAU - Dufour, Brett D AU - Dufour BD AD - Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, USA. AD - Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA. FAU - McBride, Jodi L AU - McBride JL AD - Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR, USA. mcbridej@ohsu.edu. AD - Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA. mcbridej@ohsu.edu. AD - Department of Neurology, Oregon Health and Science University, Portland, OR, USA. mcbridej@ohsu.edu. LA - eng GR - P51 OD011092/OD/NIH HHS/United States GR - P51 RR000163/RR/NCRR NIH HHS/United States GR - NS7466-14/NS/NINDS NIH HHS/United States GR - S10RR024585/RR/NCRR NIH HHS/United States GR - K01 RR000163/RR/NCRR NIH HHS/United States GR - RR000163/RR/NCRR NIH HHS/United States GR - T32 NS007466/NS/NINDS NIH HHS/United States GR - S10 RR024585/RR/NCRR NIH HHS/United States GR - P30 NS061800/NS/NINDS NIH HHS/United States GR - P51OD011092/OD/NIH HHS/United States GR - P30-NS061800/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Methods Mol Biol JT - Methods in molecular biology (Clifton, N.J.) JID - 9214969 SB - IM MH - Animals MH - Brain/cytology/*metabolism/virology MH - Dependovirus/*genetics MH - Fluorescent Antibody Technique MH - Genetic Vectors/*genetics MH - Injections MH - *Jugular Veins MH - Mice MH - *RNA Interference MH - Transduction, Genetic PMC - PMC5519340 MID - NIHMS873105 OTO - NOTNLM OT - AAV9, systemic OT - Gene therapy OT - Jugular vein OT - RNAi OT - Vascular EDAT- 2015/10/17 06:00 MHDA- 2016/04/20 06:00 PMCR- 2017/07/20 CRDT- 2015/10/17 06:00 PHST- 2015/10/17 06:00 [entrez] PHST- 2015/10/17 06:00 [pubmed] PHST- 2016/04/20 06:00 [medline] PHST- 2017/07/20 00:00 [pmc-release] AID - 10.1007/978-1-4939-3112-5_21 [doi] PST - ppublish SO - Methods Mol Biol. 2016;1364:261-75. doi: 10.1007/978-1-4939-3112-5_21.