Basic Information

Gene symbol RPE65 Synonyms BCO3, LCA2, RP20, mRPE65, p63, rd12, sRPE65 Type of gene protein-coding
Description retinoid isomerohydrolase RPE65

GTO ID GTC0132
Trial ID NCT01496040
Disease Leber Congenital Amaurosis
Altered gene RPE65
Therapeutic/Target gene Therapeutic gene
TherapyGene transfer
Treatment rAAV2/4-hRPE65
PhasePhase1|Phase2
Recruitment statusCompleted
TitleProspective Monocentric Open Label Non Randomized Uncontrolled Phase I/II Clinical Gene Therapy Protocol for the Treatment of Retinal Dystrophy Caused by Defects in RPE65
Year2011
CountryFrance
Company sponsorNantes University Hospital
Other ID(s)BRD 07/08-K|2011-000418-21
Vector information
Vectoradeno-associated virus
ConstructrAAV2/4-hRPE65
Vector typerecombinant adeno-associated virus serotype 2/4 (rAAV2/4) vector
Transgene/Inserted genehuman RPE65 coding sequence (NCBI RefSeq NM_000329)
Regulatory elementa human RPE65 promoter fragment (positions -1,359 to +23 relative to the transcription start site); a bovine growth hormone polyadenylation signal
Vector production methodFor production of the rAAV-2/4.hRPE65 vector, pAAV-hRPE65 plasmid was transfected into HEK293 cells together with pDP4-Kana helper plasmid, which provides both AAV serotype 4 rep and cap genes and adenovirus helper genes (VA RNA, E2A and E4). The vector was purified by ion-exchange chromatography and formulated in a saline solution specific for ocular surgery.

Clinical Result

Cohort 1
Administration route subretinal injection
Dosage 1.22E10~4.8E10 vg
Pts 9
Age Child, Adult
Outcome four of nine patients reported improved perception of detail, three of nine reported improved fixation, one of nine reported improved color vision, one of nine reported reduced photophobia, and one of nine reported reduced visual fatigue. Six out of nine patients presented nystagmus and four presented divergent strabismus
References PMID: 29033008

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