Development of the in vivo knockout system in the marmoset brain using AAV-PHP.B

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K14929
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Gunma University
• Principal Investigator: Matsuzaki Yasunori 群馬大学, 大学院医学系研究科, 助教 (50738200)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: アデノ随伴ウイルスベクター / AAV / マーモセット / CRISPR-Cas9

Outline of Final Research Achievements

The purpose of this study was the generation of a gene knock-out marmoset in vivo using CRISPR-Cas9 system and AAV-PHP.B which is the blood-brain barrier (BBB) high-permeable AAV vector. My preliminary experiment indicated that AAV-PHP.B drastically permeate the BBB of marmoset. However, I concluded that the permeability of AAV-PHP.B across marmoset BBB was as same as AAV9. Furthermore, I found that AAV-PHP.B cannot permeate efficiently the BBB of outbred rat and some inbred strains of mouse. I examined to obtained a new AAV vector which can significantly cross the BBB of marmoset using the CREATE method, but I had not ever discovered it.
I found a new characteristics of AAV-PHP.B, whereas I could not perform the in vivo knock-out experiment targeting a gene of marmoset brain.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、マーモセットへのin vivo knock-outまでは出来なかったが、AAV-PHP.BがマーモセットやラットではBBBを超効率的に透過できず、マウス系統においても限られた系統でのみ可能であることを明らかにすることが出来た。AAV-PHP.Bが限られた動物種でしか期待される効果が得られないという情報は研究者の実験の効率化に繋がるとともに、使用動物数の削減に繋がるため、その成果の意義は大きいと考えられる。