PMID- 33073995
OWN - NLM
STAT- MEDLINE
DCOM- 20210507
LR  - 20210507
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Linking)
VI  - 14
IP  - 11
DP  - 2020 Nov 24
TI  - Synthetically Engineered Adeno-Associated Virus for Efficient, Safe, and 
      Versatile Gene Therapy Applications.
PG  - 14262-14283
LID - 10.1021/acsnano.0c03850 [doi]
AB  - Gene therapy directly targets mutations causing disease, allowing for a specific 
      treatment at a molecular level. Adeno-associated virus (AAV) has been of 
      increasing interest as a gene delivery vehicle, as AAV vectors are safe, 
      effective, and capable of eliciting a relatively contained immune response. With 
      the recent FDA approval of two AAV drugs for treating rare genetic diseases, AAV 
      vectors are now on the market and are being further explored for other therapies. 
      While showing promise in immune privileged tissue, the use of AAV for systemic 
      delivery is still limited due to the high prevalence of neutralizing antibodies 
      (nAbs). To avoid nAb-mediated inactivation, engineered AAV vectors with modified 
      protein capsids, materials tethered to the capsid surface, or fully encapsulated 
      in a second, larger carrier have been explored. Many of these engineered AAVs 
      have added benefits, including avoided immune response, overcoming the genome 
      size limit, targeted and stimuli-responsive delivery, and multimodal therapy of 
      two or more therapeutic modalities in one platform. Native and engineered AAV 
      vectors have been tested to treat a broad range of diseases, including spinal 
      muscular atrophy, retinal diseases, cancers, and tissue damage. This review will 
      cover the benefits of AAV as a promising gene vector by itself, the progress and 
      advantages of engineered AAV vectors, particularly synthetically engineered ones, 
      and the current state of their clinical translation in therapy.
FAU - Lugin, Margaret L
AU  - Lugin ML
FAU - Lee, Rebecca T
AU  - Lee RT
FAU - Kwon, Young Jik
AU  - Kwon YJ
AUID- ORCID: 0000-0003-4086-6995
LA  - eng
GR  - R21 CA228099/CA/NCI NIH HHS/United States
GR  - T32 AI007319/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20201019
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
SB  - IM
MH  - Capsid
MH  - *Dependovirus/genetics
MH  - Gene Transfer Techniques
MH  - *Genetic Therapy
MH  - *Genetic Vectors
OTO - NOTNLM
OT  - adeno-associated virus
OT  - clinical translation
OT  - combined gene and chemotherapy
OT  - engineered AAV
OT  - gene therapy
OT  - multimodal therapy
OT  - nanoparticles
OT  - tissue engineering
EDAT- 2020/10/20 06:00
MHDA- 2021/05/08 06:00
CRDT- 2020/10/19 12:11
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2021/05/08 06:00 [medline]
PHST- 2020/10/19 12:11 [entrez]
AID - 10.1021/acsnano.0c03850 [doi]
PST - ppublish
SO  - ACS Nano. 2020 Nov 24;14(11):14262-14283. doi: 10.1021/acsnano.0c03850. Epub 2020 
      Oct 19.