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dc.contributor.authorCalkins, David J
dc.contributor.authorYu-Wai-Man, Patrick
dc.contributor.authorNewman, Nancy J
dc.contributor.authorTaiel, Magali
dc.contributor.authorSingh, Pramila
dc.contributor.authorChalmey, Clémentine
dc.contributor.authorRogue, Alexandra
dc.contributor.authorCarelli, Valerio
dc.contributor.authorAncian, Philippe
dc.contributor.authorSahel, José A
dc.date.accessioned2021-12-18T00:30:43Z
dc.date.available2021-12-18T00:30:43Z
dc.date.issued2021-12-10
dc.identifier.issn2329-0501
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331605
dc.description.abstractLenadogene nolparvovec (Lumevoq) gene therapy was developed to treat Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A in MT-ND4 that affects complex I of the mitochondrial respiratory chain. Lenadogene nolparvovec is a replication-defective, single-stranded DNA recombinant adeno-associated virus vector 2 serotype 2, containing a codon-optimized complementary DNA encoding the human wild-type MT-ND4 subunit protein. Lenadogene nolparvovec was administered by unilateral intravitreal injection in MT-ND4 LHON patients in two randomized, double-masked, and sham-controlled phase III clinical trials (REVERSE and RESCUE), resulting in bilateral improvement of visual acuity. These and other earlier results suggest that lenadogene nolparvovec may travel from the treated to the untreated eye. To investigate this possibility further, lenadogene nolparvovec was unilaterally injected into the vitreous body of the right eye of healthy, nonhuman primates. Viral vector DNA was quantifiable in all eye and optic nerve tissues of the injected eye and was detected at lower levels in some tissues of the contralateral, noninjected eye, and optic projections, at 3 and 6 months after injection. The results suggest that lenadogene nolparvovec transfers from the injected to the noninjected eye, thus providing a potential explanation for the bilateral improvement of visual function observed in the LHON patients.
dc.format.mediumElectronic-eCollection
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectLeber hereditary optic neuropathy
dc.subjectLumevoq
dc.subjectND4
dc.subjectbiodistribution
dc.subjectlenadogene nolparvovec
dc.subjectqPCR assay
dc.subjectrecombinant adeno-associated virus vector 2 serotype 2
dc.subjecttransduction
dc.subjectviral vector
dc.titleBiodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates.
dc.typeArticle
dc.publisher.departmentDepartment of Clinical Neurosciences
dc.date.updated2021-12-16T16:03:49Z
prism.endingPage318
prism.publicationDate2021
prism.publicationNameMol Ther Methods Clin Dev
prism.startingPage307
prism.volume23
dc.identifier.doi10.17863/CAM.79057
dcterms.dateAccepted2021-09-24
rioxxterms.versionofrecord10.1016/j.omtm.2021.09.013
rioxxterms.versionVoR
dc.contributor.orcidYu Wai Man, Patrick [0000-0001-7847-9320]
dc.identifier.eissn2329-0501
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Institute for Health Research (IS-BRC-1215-20014)
cam.issuedOnline2021-10
cam.depositDate2021-12-16
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International