PMID- 32857512
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20210802
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 17
IP  - 10
DP  - 2020 Oct 5
TI  - Gene Therapy: Contest between Adeno-Associated Virus and Host Cells and the 
      Impact of UFMylation.
PG  - 3649-3653
LID - 10.1021/acs.molpharmaceut.0c00512 [doi]
AB  - Adeno-associated virus (AAV)-based gene therapy is currently limited by (1) 
      decline in therapeutic gene expression over time, (2) immune cell activation and 
      (3) neutralization by pre-existing antibodies. Hence, studying the interaction of 
      AAV vectors with various cellular pathways during the production and transduction 
      process is necessary to overcome such barriers. Post-translational modifications 
      (PTM) of AAV vectors during the production and transduction process is known to 
      limit its transduction efficiency and further evoke the immune response. Further, 
      AAV vectors are known to trigger cellular stress, resulting in an upregulation of 
      distinct arms of the unfolded protein response (UPR) pathway. Recognition of the 
      AAV genome by Toll-like receptor-9 triggers the myeloid differentiation primary 
      response signaling cascade for innate (IL-6, IFN-alpha, IFN-beta) and adaptive (CD8+ 
      T-cell, B-cell) immune response against the viral capsid and the transgene 
      product. Herein, we highlight a potential intersection of the UPR, PTMs, and 
      intracellular trafficking pathways, which could be fine-tuned to augment the 
      outcome of AAV-based gene delivery.
FAU - Maurya, Shubham
AU  - Maurya S
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur 208016, India.
FAU - Jayandharan, Giridhara R
AU  - Jayandharan GR
AUID- ORCID: 0000-0001-9353-9053
AD  - Department of Biological Sciences and Bioengineering, Indian Institute of 
      Technology Kanpur, Kanpur 208016, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200828
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Capsid Proteins)
SB  - IM
MH  - Adaptive Immunity/genetics
MH  - Animals
MH  - Capsid Proteins/genetics/immunology
MH  - Dependovirus/genetics/*immunology
MH  - Genetic Therapy/*methods
MH  - Host Microbial Interactions/genetics/*immunology
MH  - Humans
MH  - Immunity, Innate/genetics
MH  - Protein Processing, Post-Translational/genetics/*immunology
MH  - Transduction, Genetic/*methods
MH  - Unfolded Protein Response/genetics/immunology
OTO - NOTNLM
OT  - UFMylation
OT  - adeno-associated virus
OT  - unfolded protein response
EDAT- 2020/08/29 06:00
MHDA- 2021/08/03 06:00
CRDT- 2020/08/29 06:00
PHST- 2020/08/29 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/08/29 06:00 [entrez]
AID - 10.1021/acs.molpharmaceut.0c00512 [doi]
PST - ppublish
SO  - Mol Pharm. 2020 Oct 5;17(10):3649-3653. doi: 10.1021/acs.molpharmaceut.0c00512. 
      Epub 2020 Aug 28.