PMID- 31991730
OWN - NLM
STAT- MEDLINE
DCOM- 20201105
LR  - 20220323
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 3
DP  - 2020 Jan 25
TI  - RNA editing as a therapeutic approach for retinal gene therapy requiring long 
      coding sequences.
LID - 10.3390/ijms21030777 [doi]
LID - 777
AB  - RNA editing aims to treat genetic disease through altering gene expression at the 
      transcript level. Pairing site-directed RNA-targeting mechanisms with engineered 
      deaminase enzymes allows for the programmable correction of G>A and T>C mutations 
      in RNA. This offers a promising therapeutic approach for a range of genetic 
      diseases. For inherited retinal degenerations caused by point mutations in large 
      genes not amenable to single-adeno-associated viral (AAV) gene therapy such as 
      USH2A and ABCA4, correcting RNA offers an alternative to gene replacement. Genome 
      editing of RNA rather than DNA may offer an improved safety profile, due to the 
      transient and potentially reversible nature of edits made to RNA. This review 
      considers the current site-directing RNA editing systems, and the potential to 
      translate these to the clinic for the treatment of inherited retinal 
      degeneration.
FAU - Fry, Lewis E
AU  - Fry LE
AD  - Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical 
      Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, 
      Oxford OX3 9DU, UK.
AD  - Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 
      9DU, UK.
FAU - Peddle, Caroline F
AU  - Peddle CF
AD  - Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical 
      Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, 
      Oxford OX3 9DU, UK.
AD  - Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 
      9DU, UK.
FAU - Barnard, Alun R
AU  - Barnard AR
AD  - Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical 
      Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, 
      Oxford OX3 9DU, UK.
AD  - Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 
      9DU, UK.
FAU - McClements, Michelle E
AU  - McClements ME
AD  - Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical 
      Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, 
      Oxford OX3 9DU, UK.
AD  - Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 
      9DU, UK.
FAU - MacLaren, Robert E
AU  - MacLaren RE
AD  - Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical 
      Neurosciences & NIHR Oxford Biomedical Research Centre, University of Oxford, 
      Oxford OX3 9DU, UK.
AD  - Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 
      9DU, UK.
LA  - eng
GR  - MC_PC_19049/MRC_/Medical Research Council/United Kingdom
GR  - NA/NIHR Oxford Biomedical Research Centre/
PT  - Journal Article
PT  - Review
DEP - 20200125
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (RNA-Binding Proteins)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
SB  - IM
MH  - Adenosine Deaminase/metabolism
MH  - Animals
MH  - CRISPR-Cas Systems
MH  - Fluorescent Antibody Technique
MH  - *Gene Editing
MH  - Gene Targeting
MH  - Genetic Diseases, Inborn/genetics/therapy
MH  - *Genetic Therapy
MH  - Humans
MH  - *RNA Editing
MH  - RNA-Binding Proteins/metabolism
MH  - Retina/*metabolism/pathology
MH  - Retinal Diseases/genetics/therapy
MH  - *Transgenes
PMC - PMC7037314
OTO - NOTNLM
OT  - ADAR
OT  - CRISPR
OT  - RNA editing
OT  - base editing
OT  - gene editing
OT  - gene therapy
OT  - genome engineering
OT  - inherited retinal degeneration
OT  - retinal disease
OT  - retinitis pigmentosa
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the manuscript.
EDAT- 2020/01/30 06:00
MHDA- 2020/11/06 06:00
PMCR- 2020/02/01
CRDT- 2020/01/30 06:00
PHST- 2019/12/19 00:00 [received]
PHST- 2020/01/20 00:00 [revised]
PHST- 2020/01/21 00:00 [accepted]
PHST- 2020/01/30 06:00 [entrez]
PHST- 2020/01/30 06:00 [pubmed]
PHST- 2020/11/06 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - ijms21030777 [pii]
AID - ijms-21-00777 [pii]
AID - 10.3390/ijms21030777 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jan 25;21(3):777. doi: 10.3390/ijms21030777.