PMID- 35941689
OWN - NLM
STAT- MEDLINE
DCOM- 20220810
LR  - 20220816
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Aug 8
TI  - The tyrosine capsid mutations on retrograde adeno-associated virus accelerates 
      gene transduction efficiency.
PG  - 70
LID - 10.1186/s13041-022-00957-0 [doi]
LID - 70
AB  - Adeno-associated virus (AAV) vector is a critical tool for gene delivery through 
      its durable transgene expression and safety profile. Among many serotypes, 
      AAV2-retro is typically utilized for dissecting neural circuits with its 
      retrograde functionality. However, this vector requires a relatively long-term 
      incubation period (over 2 weeks) to obtain enough gene expression levels 
      presumably due to low efficiency in gene transduction. Here, we aimed to enhance 
      transgene expression efficiency of AAV2-retro vectors by substituting multiple 
      tyrosine residues with phenylalanines (YF mutations) in the virus capsid, which 
      is previously reported to improve the transduction efficiency of AAV2-infected 
      cells by evading host cell responses. We found that AAV2-retro with YF mutations 
      (AAV2-retroYF)-mediated transgene expression was significantly enhanced in the 
      primary culture of murine cortical neurons at 1 week after application, 
      comparable to that of the conventional AAV2-retro at 2 week after application. 
      Moreover, transgene expressions in the retrogradely labeled neurons mediated by 
      AAV2-retroYF were significantly increased both in the cortico-cortical circuits 
      and in the subcortical circuits in vivo, while the retrograde functionality of 
      AAV2-retroYF was equally effective as that of AAV2-retro. Our data indicate that 
      YF mutations boost AAV2-retro-mediated retrograde gene transduction in vivo and 
      suggest that the AAV2-retroYF should be useful for efficient targeting of the 
      projection-defined neurons, which is suited to applications for dissecting neural 
      circuits during development as well as future clinical applications.
CI  - (c) 2022. The Author(s).
FAU - Nakahama, Ryota
AU  - Nakahama R
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
FAU - Saito, Aika
AU  - Saito A
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
FAU - Nobe, Sensho
AU  - Nobe S
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
FAU - Togashi, Kazuya
AU  - Togashi K
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
FAU - Suzuki, Ikuo K
AU  - Suzuki IK
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
FAU - Uematsu, Akira
AU  - Uematsu A
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. 
      akirauematsu0104@gmail.com.
AD  - International Research Center for Neurointelligence (WPI-IRCN), The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. 
      akirauematsu0104@gmail.com.
FAU - Emoto, Kazuo
AU  - Emoto K
AD  - Department of Biological Sciences, Graduate School of Science, The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. emoto@bs.s.u-tokyo.ac.jp.
AD  - International Research Center for Neurointelligence (WPI-IRCN), The University of 
      Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. emoto@bs.s.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220808
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 42HK56048U (Tyrosine)
SB  - IM
MH  - Animals
MH  - *Capsid
MH  - *Dependovirus/genetics
MH  - Genetic Vectors
MH  - Mice
MH  - Mutation/genetics
MH  - Transduction, Genetic
MH  - Tyrosine/genetics
PMC - PMC9358834
OTO - NOTNLM
OT  - Adeno-associated virus
OT  - Cortex
OT  - Limbic area
OT  - Monosynaptic anterograde transport
OT  - Retrograde transport
COIS- The authors declare that they have no competing interests.
EDAT- 2022/08/09 06:00
MHDA- 2022/08/11 06:00
PMCR- 2022/08/08
CRDT- 2022/08/08 23:53
PHST- 2022/05/21 00:00 [received]
PHST- 2022/07/28 00:00 [accepted]
PHST- 2022/08/08 23:53 [entrez]
PHST- 2022/08/09 06:00 [pubmed]
PHST- 2022/08/11 06:00 [medline]
PHST- 2022/08/08 00:00 [pmc-release]
AID - 10.1186/s13041-022-00957-0 [pii]
AID - 957 [pii]
AID - 10.1186/s13041-022-00957-0 [doi]
PST - epublish
SO  - Mol Brain. 2022 Aug 8;15(1):70. doi: 10.1186/s13041-022-00957-0.