In vivo gene transfer to the mouse eye using an HIV-based lentiviral vector; efficient long-term transduction of corneal endothelium and retinal pigment epithelium

Bainbridge, James; Stephens, Clare; Parsley, Kathryn L.; Demaison, Christophe; Halfyard, Anthony S; Thrasher, Adrian J.; Ali, Robin R.

doi:10.1038/sj.gt.3301574

Cited by 181 publications

(145 citation statements)

References 11 publications

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“…Use of equine infectious anaemia virus (EIAV) as a vector for gene transfer was based on previous reports of efficient and long-term gene transfer to corneal cells with lentiviral vectors [19,20]. Following IDO transduction, we detected high-level expression of IDO in MCEC at mRNA (Fig.…”

Section: Vector-mediated Ido Gene Over-expression In Corneal Endothelmentioning

confidence: 92%

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

et al. 2006

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Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-c and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts.

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Section: Vector-mediated Ido Gene Over-expression In Corneal Endothelmentioning

confidence: 92%

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

et al. 2006

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“…12,23 The lentiviral Mertk expression construct, LNT.SFFV.Mertk, was generated by cloning the murine Mertk gene between the SFFV promoter and the WPRE element of the pHR 0 SIN-cPPT-SEW lentivirus construct. 23 In total, 12 15-cm plates subconfluent with 293T cells were transfected with 50 mg of the LNT.SFFV.Mertk construct per plate together with the lentivirus helper constructs pMD.G (17.5 mg) and pCMVR8.91 (32.5 mg).…”

Section: Recombinant Lentiviral Constructsmentioning

confidence: 99%

“…Subretinal injection of lentiviral vectors results in specific and efficient transduction of RPE cells and long-term transgene expression. 12 However, the main potential advantage of using a lentiviral rather than AAV, vector in this particular model, which has a rapid degeneration, is the much faster onset of lentiviral-mediated transgene expression. Here we present a detailed assessment of the duration and extent of the morphological rescue and functional benefit following lentiviral-mediated gene replacement therapy.…”

Section: Introductionmentioning

confidence: 99%

Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy

et al. 2005

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The Royal College of Surgeons (RCS) rat is a wellcharacterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-dayold RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders. Gene Therapy (2005) 12, 694-701.

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“…21 The exclusive tropism of HSV-1 amplicon vectors for RPE cells in adult rat is similar to the tropism shown by lentiviral (HIV and SIV), rAAV1 and rAAV4 vectors. 3,13,32 Similarly to lentiviral, rAAV1 and rAAV4 vectors, intravitreal injections of HSV-1 amplicon vectors in adult rats resulted in no detectable transduction (data not shown).…”

mentioning

confidence: 92%

“…[1][2][3] Until now, efficient long-term gene transfer was documented only for the AAV and lentiviral-based vectors.…”

mentioning

confidence: 99%

In vivo gene transfer to the rat retina using herpes simplex virus type 1 (HSV-1)-based amplicon vectors

et al. 2005

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The purpose of our study was to evaluate the transduction profiles of herpes simplex virus type 1 (HSV-1)-based amplicon vectors following subretinal injection in the rat. Two amplicon vectors were tested, pHy-CMVGFP and pHy-RPEGFP, both carrying the green fluorescent protein (GFP) under the control of the cytomegalovirus (CMV) ubiquitous promoter or the RPE65-specific promoter, respectively. For the two amplicon vectors, the GFP reporter gene was efficiently expressed in retinal pigment epithelial (RPE) cells but not in the adjacent photoreceptors. GFP expression was maximum as early as 2 days postadministration but decreased over time to become almost undetectable at 6 weeks postinjection. Supertransduction with a second amplicon vector, pHSVlac, reactivated expression of GFP in approximately 10% of the cells initially transduced at 2 days postinjection of pHy-CMVGFP or pHy-RPEGFP. Reactivation of transgene expression was transient, no GFP signal was detected 8 days after pHSVlac injection. In conclusion, HSV-1 amplicon vectors allow rapid and efficient, but transient, gene transfer in RPE cells following subretinal injection.

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In vivo gene transfer to the mouse eye using an HIV-based lentiviral vector; efficient long-term transduction of corneal endothelium and retinal pigment epithelium

Cited by 181 publications

References 11 publications

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

Function of indoleamine 2,3‐dioxygenase in corneal allograft rejection and prolongation of allograft survival by over‐expression

Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy

In vivo gene transfer to the rat retina using herpes simplex virus type 1 (HSV-1)-based amplicon vectors

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