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פותח על ידי קלירמאש פתרונות בע"מ -
Evaluation of photoreceptor transduction efficacy of capsid-modified Adeno-Associated Viral vectors following intravitreal and subretinal delivery in sheep
Year:
2020
Authors :
גוטויין, אלישע
;
.
דביר, חי
;
.
הניג, חן
;
.
רוזוב, אלכסנדר
;
.
Volume :
Co-Authors:

Maya Ross  - Hebrew University of Jerusalem, 26742, Koret School of Veterinary Medicine, Rehovot, Israel. 
Alexey Obolensky 
- Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel.  
Edward Averbukh  Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel
. 
Raaya Ezra-Elia  - Hebrew University of Jerusalem, Koret School of Veterinary medicine, Rehovot, Israel.
Esther Yamin  - Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel.
William W Hauswirth  - University of Florida, 3463, Department of Ophthalmology, Gainesville, Florida, United States.
Eyal Banin  - Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel.
Ron Ofri  - Hebrew University of Jerusalem, Koret School of Veterinary medicine, Rehovot, Israel.

Facilitators :
From page:
0
To page:
0
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Total pages:
1
)
Abstract:

Gene augmentation therapy based on subretinal delivery of Adeno-Associated Viral (AAV) vectors is proving to be highly efficient in treating several inherited retinal degenerations. However, due to potential complications and drawbacks posed by subretinal injections, there is a great impetus to find alternative methods of delivering the desired genetic inserts to the retina. One such method is an intravitreal delivery of the vector. Our aim was to evaluate the efficacy of two capsid modified vectors that are less susceptible to cellular degradation, AAV8 (doubleY-F) and AAV2 (quadY-F+T-V), as well as a third, chimeric vector AAV[max], to transduce photoreceptor cells following intravitreal injection in sheep. We further tested whether saturation of inner limiting membrane (ILM) viral binding sites using a non-modified vector, prior to the intravitreal injection, would enhance the efficacy of photoreceptor transduction. Only AAV[max] resulted in moderate photoreceptor transduction following intravitreal injection. Intravitreal injection of the two other vectors did not result in photoreceptor transduction, nor did the saturation of the ILM prior to the intravitreal injection. On the other hand, two of the vectors efficiently transduced photoreceptor cells following subretinal injection in positive control eyes. Previous trials with the same vectors in both murine and canine models resulted in robust and moderate transduction efficacy, respectively, of photoreceptors following intravitreal delivery, demonstrating the importance of utilizing as many animal models as possible when evaluating new strategies for retinal gene therapy. The successful photoreceptor transduction of AAV[max] injected intravitreally makes it a potential candidate for intravitreal delivery, but further trials are warranted to determine whether the transduction efficacy is sufficient for a clinical outcome.

Note:
Related Files :
capsid-modified AAV vectors
Photoreceptors
photoreceptor transduction efficacy
retina
sheep
עוד תגיות
תוכן קשור
More details
DOI :
10.1089/hum.2020.023
Article number:
0
Affiliations:
Database:
PubMed
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
48116
Last updated date:
02/03/2022 17:27
Creation date:
08/06/2020 17:37
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Scientific Publication
Evaluation of photoreceptor transduction efficacy of capsid-modified Adeno-Associated Viral vectors following intravitreal and subretinal delivery in sheep

Maya Ross  - Hebrew University of Jerusalem, 26742, Koret School of Veterinary Medicine, Rehovot, Israel. 
Alexey Obolensky 
- Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel.  
Edward Averbukh  Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel
. 
Raaya Ezra-Elia  - Hebrew University of Jerusalem, Koret School of Veterinary medicine, Rehovot, Israel.
Esther Yamin  - Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel.
William W Hauswirth  - University of Florida, 3463, Department of Ophthalmology, Gainesville, Florida, United States.
Eyal Banin  - Hadassah University Hospital, 58884, Department of Ophthalmology, Jerusalem, Israel.
Ron Ofri  - Hebrew University of Jerusalem, Koret School of Veterinary medicine, Rehovot, Israel.

Evaluation of photoreceptor transduction efficacy of capsid-modified AAV vectors following intravitreal and subretinal delivery in sheep

Gene augmentation therapy based on subretinal delivery of Adeno-Associated Viral (AAV) vectors is proving to be highly efficient in treating several inherited retinal degenerations. However, due to potential complications and drawbacks posed by subretinal injections, there is a great impetus to find alternative methods of delivering the desired genetic inserts to the retina. One such method is an intravitreal delivery of the vector. Our aim was to evaluate the efficacy of two capsid modified vectors that are less susceptible to cellular degradation, AAV8 (doubleY-F) and AAV2 (quadY-F+T-V), as well as a third, chimeric vector AAV[max], to transduce photoreceptor cells following intravitreal injection in sheep. We further tested whether saturation of inner limiting membrane (ILM) viral binding sites using a non-modified vector, prior to the intravitreal injection, would enhance the efficacy of photoreceptor transduction. Only AAV[max] resulted in moderate photoreceptor transduction following intravitreal injection. Intravitreal injection of the two other vectors did not result in photoreceptor transduction, nor did the saturation of the ILM prior to the intravitreal injection. On the other hand, two of the vectors efficiently transduced photoreceptor cells following subretinal injection in positive control eyes. Previous trials with the same vectors in both murine and canine models resulted in robust and moderate transduction efficacy, respectively, of photoreceptors following intravitreal delivery, demonstrating the importance of utilizing as many animal models as possible when evaluating new strategies for retinal gene therapy. The successful photoreceptor transduction of AAV[max] injected intravitreally makes it a potential candidate for intravitreal delivery, but further trials are warranted to determine whether the transduction efficacy is sufficient for a clinical outcome.

Scientific Publication
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