Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.
Identifieur interne : 000353 ( Main/Exploration ); précédent : 000352; suivant : 000354Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.
Auteurs : Steven Hyun Seung Lee [Corée du Sud] ; Heesoon Chang [Corée du Sud] ; Hee Jong Kim [Corée du Sud] ; Jun-Sub Choi [Corée du Sud] ; Jin Kim [Corée du Sud] ; Ji Hyun Kim [Corée du Sud] ; Ha-Na Woo [Corée du Sud] ; Seung Kwan Nah [Corée du Sud] ; Sang Joon Jung [Corée du Sud] ; Joo Yong Lee [Corée du Sud] ; Keerang Park [Corée du Sud] ; Tae Kwann Park [Corée du Sud] ; Heuiran Lee [Corée du Sud]Source :
- Molecular therapy. Methods & clinical development [ 2329-0501 ] ; 2019.
Abstract
Choroidal neovascularization (CNV) is the defining characteristic of the wet subtype of age-related macular degeneration (AMD), which is a rapidly growing global health problem. Previously, we had demonstrated the therapeutic potential of gene therapy against CNV using short hairpin RNA (shRNA) delivered via recombinant adeno-associated virus (rAAV), which abrogates mammalian-to-mechanistic (mTOR) activity in a novel manner by simultaneously inhibiting both mTOR complexes. Both the target and use of gene therapy represent a novel treatment modality against AMD. Here, the xenogeneic GFP gene used as a reporter in previous studies was removed from the virus vector to further develop the therapeutic for clinical trials. Instead, a stuffer DNA derived from the 3' UTR of the human UBE3A gene was used to ensure optimal viral genome size for efficient rAAV assembly. The virus vector containing the stuffer DNA, rAAV2-shmTOR-SD, positively compares to one encoding the shRNA and a GFP expression cassette in terms of reducing CNV in a laser-induced mouse model, as determined by fundus fluorescein angiography. These results were confirmed via immunohistochemistry using anti-CD31, while a TUNEL assay showed that rAAV2-shmTOR-SD possesses anti-apoptotic properties as well. The qualities exhibited by rAAV2-shmTOR-SD demonstrate its potential as a human gene therapeutic for the treatment of wet AMD.
DOI: 10.1016/j.omtm.2019.06.004
PubMed: 31380463
PubMed Central: PMC6661460
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.</title><author><name sortKey="Lee, Steven Hyun Seung" sort="Lee, Steven Hyun Seung" uniqKey="Lee S" first="Steven Hyun Seung" last="Lee">Steven Hyun Seung Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Chang, Heesoon" sort="Chang, Heesoon" uniqKey="Chang H" first="Heesoon" last="Chang">Heesoon Chang</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Hee Jong" sort="Kim, Hee Jong" uniqKey="Kim H" first="Hee Jong" last="Kim">Hee Jong Kim</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Jun Sub" sort="Choi, Jun Sub" uniqKey="Choi J" first="Jun-Sub" last="Choi">Jun-Sub Choi</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Jin" sort="Kim, Jin" uniqKey="Kim J" first="Jin" last="Kim">Jin Kim</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Ji Hyun" sort="Kim, Ji Hyun" uniqKey="Kim J" first="Ji Hyun" last="Kim">Ji Hyun Kim</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Woo, Ha Na" sort="Woo, Ha Na" uniqKey="Woo H" first="Ha-Na" last="Woo">Ha-Na Woo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Nah, Seung Kwan" sort="Nah, Seung Kwan" uniqKey="Nah S" first="Seung Kwan" last="Nah">Seung Kwan Nah</name><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584</wicri:regionArea><wicri:noRegion>Bucheon 14584</wicri:noRegion></affiliation></author><author><name sortKey="Jung, Sang Joon" sort="Jung, Sang Joon" uniqKey="Jung S" first="Sang Joon" last="Jung">Sang Joon Jung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584</wicri:regionArea><wicri:noRegion>Bucheon 14584</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Joo Yong" sort="Lee, Joo Yong" uniqKey="Lee J" first="Joo Yong" last="Lee">Joo Yong Lee</name><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, University of Ulsan, College of Medicine, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, University of Ulsan, College of Medicine, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Park, Keerang" sort="Park, Keerang" uniqKey="Park K" first="Keerang" last="Park">Keerang Park</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biopharmacy, Chungbuk Health & Science University, Cheongju 28150, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biopharmacy, Chungbuk Health & Science University, Cheongju 28150</wicri:regionArea><wicri:noRegion>Cheongju 28150</wicri:noRegion></affiliation></author><author><name sortKey="Park, Tae Kwann" sort="Park, Tae Kwann" uniqKey="Park T" first="Tae Kwann" last="Park">Tae Kwann Park</name><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584</wicri:regionArea><wicri:noRegion>Bucheon 14584</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151</wicri:regionArea><wicri:noRegion>Cheonan 31151</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Heuiran" sort="Lee, Heuiran" uniqKey="Lee H" first="Heuiran" last="Lee">Heuiran Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:31380463</idno><idno type="pmid">31380463</idno><idno type="doi">10.1016/j.omtm.2019.06.004</idno><idno type="pmc">PMC6661460</idno><idno type="wicri:Area/Main/Corpus">000218</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000218</idno><idno type="wicri:Area/Main/Curation">000218</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000218</idno><idno type="wicri:Area/Main/Exploration">000218</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.</title><author><name sortKey="Lee, Steven Hyun Seung" sort="Lee, Steven Hyun Seung" uniqKey="Lee S" first="Steven Hyun Seung" last="Lee">Steven Hyun Seung Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Chang, Heesoon" sort="Chang, Heesoon" uniqKey="Chang H" first="Heesoon" last="Chang">Heesoon Chang</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Hee Jong" sort="Kim, Hee Jong" uniqKey="Kim H" first="Hee Jong" last="Kim">Hee Jong Kim</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Jun Sub" sort="Choi, Jun Sub" uniqKey="Choi J" first="Jun-Sub" last="Choi">Jun-Sub Choi</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Jin" sort="Kim, Jin" uniqKey="Kim J" first="Jin" last="Kim">Jin Kim</name><affiliation wicri:level="1"><nlm:affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>CuroGene Life Sciences Co., Ltd., Cheongju 28578</wicri:regionArea><wicri:noRegion>Cheongju 28578</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Ji Hyun" sort="Kim, Ji Hyun" uniqKey="Kim J" first="Ji Hyun" last="Kim">Ji Hyun Kim</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Woo, Ha Na" sort="Woo, Ha Na" uniqKey="Woo H" first="Ha-Na" last="Woo">Ha-Na Woo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Nah, Seung Kwan" sort="Nah, Seung Kwan" uniqKey="Nah S" first="Seung Kwan" last="Nah">Seung Kwan Nah</name><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584</wicri:regionArea><wicri:noRegion>Bucheon 14584</wicri:noRegion></affiliation></author><author><name sortKey="Jung, Sang Joon" sort="Jung, Sang Joon" uniqKey="Jung S" first="Sang Joon" last="Jung">Sang Joon Jung</name><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584</wicri:regionArea><wicri:noRegion>Bucheon 14584</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Joo Yong" sort="Lee, Joo Yong" uniqKey="Lee J" first="Joo Yong" last="Lee">Joo Yong Lee</name><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, University of Ulsan, College of Medicine, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, University of Ulsan, College of Medicine, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Park, Keerang" sort="Park, Keerang" uniqKey="Park K" first="Keerang" last="Park">Keerang Park</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biopharmacy, Chungbuk Health & Science University, Cheongju 28150, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Biopharmacy, Chungbuk Health & Science University, Cheongju 28150</wicri:regionArea><wicri:noRegion>Cheongju 28150</wicri:noRegion></affiliation></author><author><name sortKey="Park, Tae Kwann" sort="Park, Tae Kwann" uniqKey="Park T" first="Tae Kwann" last="Park">Tae Kwann Park</name><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584</wicri:regionArea><wicri:noRegion>Bucheon 14584</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:affiliation>Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151</wicri:regionArea><wicri:noRegion>Cheonan 31151</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Heuiran" sort="Lee, Heuiran" uniqKey="Lee H" first="Heuiran" last="Lee">Heuiran Lee</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author></analytic><series><title level="j">Molecular therapy. Methods & clinical development</title><idno type="ISSN">2329-0501</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Choroidal neovascularization (CNV) is the defining characteristic of the wet subtype of age-related macular degeneration (AMD), which is a rapidly growing global health problem. Previously, we had demonstrated the therapeutic potential of gene therapy against CNV using short hairpin RNA (shRNA) delivered via recombinant adeno-associated virus (rAAV), which abrogates mammalian-to-mechanistic (mTOR) activity in a novel manner by simultaneously inhibiting both mTOR complexes. Both the target and use of gene therapy represent a novel treatment modality against AMD. Here, the xenogeneic GFP gene used as a reporter in previous studies was removed from the virus vector to further develop the therapeutic for clinical trials. Instead, a stuffer DNA derived from the 3' UTR of the human UBE3A gene was used to ensure optimal viral genome size for efficient rAAV assembly. The virus vector containing the stuffer DNA, rAAV2-shmTOR-SD, positively compares to one encoding the shRNA and a GFP expression cassette in terms of reducing CNV in a laser-induced mouse model, as determined by fundus fluorescein angiography. These results were confirmed via immunohistochemistry using anti-CD31, while a TUNEL assay showed that rAAV2-shmTOR-SD possesses anti-apoptotic properties as well. The qualities exhibited by rAAV2-shmTOR-SD demonstrate its potential as a human gene therapeutic for the treatment of wet AMD.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">31380463</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>01</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2329-0501</ISSN><JournalIssue CitedMedium="Print"><Volume>14</Volume><PubDate><Year>2019</Year><Month>Sep</Month><Day>13</Day></PubDate></JournalIssue><Title>Molecular therapy. Methods & clinical development</Title><ISOAbbreviation>Mol Ther Methods Clin Dev</ISOAbbreviation></Journal><ArticleTitle>Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.</ArticleTitle><Pagination><MedlinePgn>171-179</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.omtm.2019.06.004</ELocationID><Abstract><AbstractText>Choroidal neovascularization (CNV) is the defining characteristic of the wet subtype of age-related macular degeneration (AMD), which is a rapidly growing global health problem. Previously, we had demonstrated the therapeutic potential of gene therapy against CNV using short hairpin RNA (shRNA) delivered via recombinant adeno-associated virus (rAAV), which abrogates mammalian-to-mechanistic (mTOR) activity in a novel manner by simultaneously inhibiting both mTOR complexes. Both the target and use of gene therapy represent a novel treatment modality against AMD. Here, the xenogeneic GFP gene used as a reporter in previous studies was removed from the virus vector to further develop the therapeutic for clinical trials. Instead, a stuffer DNA derived from the 3' UTR of the human UBE3A gene was used to ensure optimal viral genome size for efficient rAAV assembly. The virus vector containing the stuffer DNA, rAAV2-shmTOR-SD, positively compares to one encoding the shRNA and a GFP expression cassette in terms of reducing CNV in a laser-induced mouse model, as determined by fundus fluorescein angiography. These results were confirmed via immunohistochemistry using anti-CD31, while a TUNEL assay showed that rAAV2-shmTOR-SD possesses anti-apoptotic properties as well. The qualities exhibited by rAAV2-shmTOR-SD demonstrate its potential as a human gene therapeutic for the treatment of wet AMD.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Steven Hyun Seung</ForeName><Initials>SHS</Initials><AffiliationInfo><Affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>HeeSoon</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Hee Jong</ForeName><Initials>HJ</Initials><AffiliationInfo><Affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Choi</LastName><ForeName>Jun-Sub</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Jin</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>CuroGene Life Sciences Co., Ltd., Cheongju 28578, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Ji Hyun</ForeName><Initials>JH</Initials><AffiliationInfo><Affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Woo</LastName><ForeName>Ha-Na</ForeName><Initials>HN</Initials><AffiliationInfo><Affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nah</LastName><ForeName>Seung Kwan</ForeName><Initials>SK</Initials><AffiliationInfo><Affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jung</LastName><ForeName>Sang Joon</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Joo Yong</ForeName><Initials>JY</Initials><AffiliationInfo><Affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Ophthalmology, University of Ulsan, College of Medicine, Seoul 05505, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Keerang</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Biopharmacy, Chungbuk Health & Science University, Cheongju 28150, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Tae Kwann</ForeName><Initials>TK</Initials><AffiliationInfo><Affiliation>Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, Bucheon 14584, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Heuiran</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Microbiology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Bio-Medical Institute of Technology, College of Medicine, University of Ulsan, Seoul 05505, Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>07</Month><Day>03</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Mol Ther Methods Clin Dev</MedlineTA><NlmUniqueID>101624857</NlmUniqueID><ISSNLinking>2329-0501</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">GFP</Keyword><Keyword MajorTopicYN="N">RNAi</Keyword><Keyword MajorTopicYN="N">choroidal neovascularization</Keyword><Keyword MajorTopicYN="N">mammalian target of rapamycin</Keyword><Keyword MajorTopicYN="N">recombinant adeno-associated virus</Keyword><Keyword MajorTopicYN="N">stuffer DNA</Keyword><Keyword MajorTopicYN="N">wet age-related macular degeneration</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>02</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>06</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>8</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>8</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>8</Month><Day>6</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31380463</ArticleId><ArticleId IdType="doi">10.1016/j.omtm.2019.06.004</ArticleId><ArticleId IdType="pii">S2329-0501(19)30065-8</ArticleId><ArticleId IdType="pmc">PMC6661460</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Biochem Biophys Res Commun. 1999 Jul 14;260(3):712-7</Citation><ArticleIdList><ArticleId IdType="pubmed">10403831</ArticleId></ArticleIdList></Reference><Reference><Citation>J Virol. 1999 Oct;73(10):8027-34</Citation><ArticleIdList><ArticleId IdType="pubmed">10482551</ArticleId></ArticleIdList></Reference><Reference><Citation>Gene Ther. 2000 Dec;7(23):2036-40</Citation><ArticleIdList><ArticleId IdType="pubmed">11175316</ArticleId></ArticleIdList></Reference><Reference><Citation>Blood. 2001 Apr 1;97(7):1951-9</Citation><ArticleIdList><ArticleId IdType="pubmed">11264158</ArticleId></ArticleIdList></Reference><Reference><Citation>Mol Vis. 2004 Dec 22;10:964-72</Citation><ArticleIdList><ArticleId IdType="pubmed">15623986</ArticleId></ArticleIdList></Reference><Reference><Citation>Methods Enzymol. 2005;392:381-405</Citation><ArticleIdList><ArticleId IdType="pubmed">15644194</ArticleId></ArticleIdList></Reference><Reference><Citation>Pharmacol Rep. 2006 May-Jun;58(3):353-63</Citation><ArticleIdList><ArticleId IdType="pubmed">16845209</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2006 Dec 20;1:e54</Citation><ArticleIdList><ArticleId IdType="pubmed">17183684</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Gene Ther. 2007 Feb;18(2):171-82</Citation><ArticleIdList><ArticleId IdType="pubmed">17328683</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Pathol. 2007 Jul;171(1):53-67</Citation><ArticleIdList><ArticleId IdType="pubmed">17591953</ArticleId></ArticleIdList></Reference><Reference><Citation>Front Biosci. 2008 Jan 01;13:2653-9</Citation><ArticleIdList><ArticleId IdType="pubmed">17981740</ArticleId></ArticleIdList></Reference><Reference><Citation>J Biomed Biotechnol. 2008;2008:453590</Citation><ArticleIdList><ArticleId IdType="pubmed">18401450</ArticleId></ArticleIdList></Reference><Reference><Citation>FEBS Lett. 2008 Sep 3;582(20):3097-102</Citation><ArticleIdList><ArticleId IdType="pubmed">18703055</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2008;3(11):e3554</Citation><ArticleIdList><ArticleId IdType="pubmed">18978936</ArticleId></ArticleIdList></Reference><Reference><Citation>Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4279-87</Citation><ArticleIdList><ArticleId IdType="pubmed">19357358</ArticleId></ArticleIdList></Reference><Reference><Citation>Biochem Biophys Res Commun. 2009 Jul 10;384(4):431-5</Citation><ArticleIdList><ArticleId IdType="pubmed">19422797</ArticleId></ArticleIdList></Reference><Reference><Citation>Ophthalmology. 2012 Jun;119(6):1175-83</Citation><ArticleIdList><ArticleId IdType="pubmed">22306121</ArticleId></ArticleIdList></Reference><Reference><Citation>Methods Enzymol. 2012;507:229-54</Citation><ArticleIdList><ArticleId IdType="pubmed">22365777</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2012 Apr 13;149(2):274-93</Citation><ArticleIdList><ArticleId IdType="pubmed">22500797</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell Mol Life Sci. 2012 Sep;69(18):3147-58</Citation><ArticleIdList><ArticleId IdType="pubmed">22562582</ArticleId></ArticleIdList></Reference><Reference><Citation>FEBS Open Bio. 2012 Dec 19;3:46-50</Citation><ArticleIdList><ArticleId IdType="pubmed">23772373</ArticleId></ArticleIdList></Reference><Reference><Citation>PLoS One. 2014 Feb 26;9(2):e88203</Citation><ArticleIdList><ArticleId IdType="pubmed">24586308</ArticleId></ArticleIdList></Reference><Reference><Citation>Lancet Glob Health. 2014 Feb;2(2):e106-16</Citation><ArticleIdList><ArticleId IdType="pubmed">25104651</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Respir Cell Mol Biol. 2015 Sep;53(3):291-302</Citation><ArticleIdList><ArticleId IdType="pubmed">25845025</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Gene Ther Methods. 2015 Oct;26(5):159-61</Citation><ArticleIdList><ArticleId IdType="pubmed">26413863</ArticleId></ArticleIdList></Reference><Reference><Citation>Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8314-24</Citation><ArticleIdList><ArticleId IdType="pubmed">26720485</ArticleId></ArticleIdList></Reference><Reference><Citation>Stem Cell Rev Rep. 2016 Oct;12(5):553-559</Citation><ArticleIdList><ArticleId IdType="pubmed">27435468</ArticleId></ArticleIdList></Reference><Reference><Citation>Am J Ophthalmol. 2017 May;177:150-158</Citation><ArticleIdList><ArticleId IdType="pubmed">28245970</ArticleId></ArticleIdList></Reference><Reference><Citation>Cell. 2017 Mar 9;168(6):960-976</Citation><ArticleIdList><ArticleId IdType="pubmed">28283069</ArticleId></ArticleIdList></Reference><Reference><Citation>Redox Biol. 2017 Aug;12:462-468</Citation><ArticleIdList><ArticleId IdType="pubmed">28334681</ArticleId></ArticleIdList></Reference><Reference><Citation>Mol Ther Nucleic Acids. 2017 Sep 15;8:26-35</Citation><ArticleIdList><ArticleId IdType="pubmed">28918027</ArticleId></ArticleIdList></Reference><Reference><Citation>Biol Pharm Bull. 2017;40(12):2045-2049</Citation><ArticleIdList><ArticleId IdType="pubmed">29199229</ArticleId></ArticleIdList></Reference><Reference><Citation>Pharmaceutics. 2018 Jan 27;10(1):null</Citation><ArticleIdList><ArticleId IdType="pubmed">29382038</ArticleId></ArticleIdList></Reference><Reference><Citation>J Curr Ophthalmol. 2018 Feb 16;30(1):1-2</Citation><ArticleIdList><ArticleId IdType="pubmed">29564403</ArticleId></ArticleIdList></Reference><Reference><Citation>EMBO J. 1996 Sep 16;15(18):4919-27</Citation><ArticleIdList><ArticleId IdType="pubmed">8890165</ArticleId></ArticleIdList></Reference><Reference><Citation>Hum Gene Ther. 1996 Nov 10;7(17):2101-12</Citation><ArticleIdList><ArticleId IdType="pubmed">8934224</ArticleId></ArticleIdList></Reference><Reference><Citation>Genes Dev. 1998 Mar 15;12(6):806-19</Citation><ArticleIdList><ArticleId IdType="pubmed">9512515</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Lee, Steven Hyun Seung" sort="Lee, Steven Hyun Seung" uniqKey="Lee S" first="Steven Hyun Seung" last="Lee">Steven Hyun Seung Lee</name></region><name sortKey="Chang, Heesoon" sort="Chang, Heesoon" uniqKey="Chang H" first="Heesoon" last="Chang">Heesoon Chang</name><name sortKey="Choi, Jun Sub" sort="Choi, Jun Sub" uniqKey="Choi J" first="Jun-Sub" last="Choi">Jun-Sub Choi</name><name sortKey="Jung, Sang Joon" sort="Jung, Sang Joon" uniqKey="Jung S" first="Sang Joon" last="Jung">Sang Joon Jung</name><name sortKey="Kim, Hee Jong" sort="Kim, Hee Jong" uniqKey="Kim H" first="Hee Jong" last="Kim">Hee Jong Kim</name><name sortKey="Kim, Ji Hyun" sort="Kim, Ji Hyun" uniqKey="Kim J" first="Ji Hyun" last="Kim">Ji Hyun Kim</name><name sortKey="Kim, Ji Hyun" sort="Kim, Ji Hyun" uniqKey="Kim J" first="Ji Hyun" last="Kim">Ji Hyun Kim</name><name sortKey="Kim, Jin" sort="Kim, Jin" uniqKey="Kim J" first="Jin" last="Kim">Jin Kim</name><name sortKey="Lee, Heuiran" sort="Lee, Heuiran" uniqKey="Lee H" first="Heuiran" last="Lee">Heuiran Lee</name><name sortKey="Lee, Heuiran" sort="Lee, Heuiran" uniqKey="Lee H" first="Heuiran" last="Lee">Heuiran Lee</name><name sortKey="Lee, Joo Yong" sort="Lee, Joo Yong" uniqKey="Lee J" first="Joo Yong" last="Lee">Joo Yong Lee</name><name sortKey="Lee, Joo Yong" sort="Lee, Joo Yong" uniqKey="Lee J" first="Joo Yong" last="Lee">Joo Yong Lee</name><name sortKey="Lee, Joo Yong" sort="Lee, Joo Yong" uniqKey="Lee J" first="Joo Yong" last="Lee">Joo Yong Lee</name><name sortKey="Lee, Steven Hyun Seung" sort="Lee, Steven Hyun Seung" uniqKey="Lee S" first="Steven Hyun Seung" last="Lee">Steven Hyun Seung Lee</name><name sortKey="Nah, Seung Kwan" sort="Nah, Seung Kwan" uniqKey="Nah S" first="Seung Kwan" last="Nah">Seung Kwan Nah</name><name sortKey="Park, Keerang" sort="Park, Keerang" uniqKey="Park K" first="Keerang" last="Park">Keerang Park</name><name sortKey="Park, Tae Kwann" sort="Park, Tae Kwann" uniqKey="Park T" first="Tae Kwann" last="Park">Tae Kwann Park</name><name sortKey="Park, Tae Kwann" sort="Park, Tae Kwann" uniqKey="Park T" first="Tae Kwann" last="Park">Tae Kwann Park</name><name sortKey="Woo, Ha Na" sort="Woo, Ha Na" uniqKey="Woo H" first="Ha-Na" last="Woo">Ha-Na Woo</name><name sortKey="Woo, Ha Na" sort="Woo, Ha Na" uniqKey="Woo H" first="Ha-Na" last="Woo">Ha-Na Woo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Bois/explor/RapamycinFungusV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000353 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000353 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Bois
|area= RapamycinFungusV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:31380463
|texte= Effects of Stuffer DNA on the Suppression of Choroidal Neovascularization by a rAAV Expressing a mTOR-Inhibiting shRNA.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:31380463" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a RapamycinFungusV1
| This area was generated with Dilib version V0.6.38. |  |