Development of photoreceptor‐specific promoters and their utility to investigate EIAV lentiviral vector mediated gene transfer to photoreceptors

Nicoud, Marjorie; Kong, Jian; Iqball, Sharifah; Kan, On; Naylor, Stuart; Gouras, Peter; Allikmets, Rando; Binley, Katie

doi:10.1002/jgm.1115

Cited by 20 publications

(23 citation statements)

References 34 publications

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“…5,6 OCULAR TRANSDUCTION PROFILES OF LENTIVIRAL VECTORS The transduction properties of HIV-1, (refs 7-24) HIV-2, (ref. 25) SIV, [26][27][28][29] EIAV, 21,[30][31][32][33][34][35] FIV, 24,[36][37][38][39][40][41][42][43] and BIV 44 vectors incorporating a diverse array of envelope pseudotypes and transgene promoters have been evaluated after in vivo and ex vivo delivery in a variety of animal species (Supplementary Tables 1 and 2). Most ocular studies have used vesicular stomatitis virus-G (VSV-G)-pseudotyped vectors incorporating ubiquitous promoters and these are described below unless otherwise stated.…”

Section: Introductionmentioning

confidence: 99%

Ocular gene delivery using lentiviral vectors

Balaggan

Ali²

2011

Gene Ther

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Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable for gene delivery in ophthalmic diseases, including high expression, consistent targeting of various post-mitotic ocular cells in vivo and a paucity of associated intraocular inflammation, all contributing to their ability to mediate efficient and stable intraocular gene transfer. In this review, the intraocular tropisms and therapeutic applications of both primate and non-primate lentiviral vectors, and how the unique features of the eye influence these, are discussed. The feasibility of therapeutic targeting using these vectors in animal models of both anterior and posterior ophthalmic disorders has been established, and has, in combination with substantial progress in enhancing lentiviral vector bio-safety over the past two decades, paved the way for the first human ophthalmic clinical trials using lentivirus-based gene transfer vectors.

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Section: Introductionmentioning

confidence: 99%

Ocular gene delivery using lentiviral vectors

Balaggan

Ali²

2011

Gene Ther

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“…Most studies showed that following SR delivery, LVs transduce the RPE efficiently in rodents (Auricchio et al, 2001;Bainbridge et al, 2001;Duisit et al, 2002;Kachi et al, 2009), but PRs variably and inadequately (Miyoshi et al, 1997;Bemelmans et al, 2005;Balaggan et al, 2006). Notably, PR transduction by LVs is inversely correlated to PR differentiation (Miyoshi et al, 1997;Bainbridge et al, 2001;Pang et al, 2006;Nicoud et al, 2007). Consistent with these observations, the SR delivery of LVs to the adult retina was effective in rodent models of IR caused by mutations in genes expressed in the RPE (Vollrath et al, 2001;Bemelmans et al, 2006), whereas perinatal (Takahashi et al, 1999;Hashimoto et al, 2007;Kong et al, 2008) or in utero (Williams et al, 2006) deliveries were required to treat rodent models that bear mutations in genes expressed in PRs.…”

Section: Efficient Viral Vectors Are Key Elements For Successful Retimentioning

confidence: 99%

Gene Therapy of Inherited Retinopathies: A Long and Successful Road from Viral Vectors to Patients

Colella

Auricchio

2012

Human Gene Therapy

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“…Attempts to improve neuronal targeting by employing pseudotypes derived from neurotropic viruses, such as rabies-G (Balaggan et al, 2006) or mokola (Bemelmans et al, 2005), have met with little success. Similarly, while photoreceptor-specific promoters have been successfully incorporated into both HIV and EIAV vectors, they effectively limit ectopic expression of the transgene, but do not significantly increase the levels of photoreceptor transduction in the adult retina (Miyoshi et al, 1997;Nicoud et al, 2007). Herein, we employ longitudinal in vivo fluorescence imaging to examine the tropism of a further pseudotype derived from Venezuelan equine encephalitis virus (VEEV-G), a zoonotic virus that causes encephalopathy in various equine species and humans.…”

Section: Introductionmentioning

confidence: 97%

Vesicular Stomatitis Virus Glycoprotein– and Venezuelan Equine Encephalitis Virus-Derived Glycoprotein–Pseudotyped Lentivirus Vectors Differentially Transduce Corneal Endothelium, Trabecular Meshwork, and Human Photoreceptors

et al. 2014

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The ability to deliver a large transgene efficiently to photoreceptors using viral vectors remains problematic and yet is critical for the future therapy of inherited retinal diseases such as Stargardt's and Usher's 1B. Herein, we examine the ocular tropism of a HIV-1-based lentivirus vector pseudotyped with Venezuelan equine encephalitis virus-derived glycoprotein (VEEV-G) after intraocular delivery to the posterior and anterior chambers of C57BL/6 wild-type mice. Reporter gene (EGFP) expression was evaluated using in vivo fluorescence imaging followed by postmortem immunohistochemistry and retinal function assessed by electroretinography. Intracameral administration of VEEV-G and vesicular stomatitis virus glycoprotein (VSV-G)-pseudotyped vectors resulted in robust transgene expression in the corneal endothelium and trabecular meshwork. After subretinal administration, onset of transgene expression was observed in the retinal pigment epithelium (RPE) 1 day postinjection with both VEEV-G and control VSV-G pseudotypes, but no significant photoreceptor transduction was apparent. Substantial degeneration of the outer nuclear layer was observed with VEEV-G-pseudotyped vector, which corresponded to ablation of retinal function. Subretinal administration of VSV-G was observed to result in significant suppression of electrophysiological function compared with buffer-injected and uninjected control eyes. Suppression of the c-wave amplitude, in addition to reduced RPE65 expression, indicated potential RPE dysfunction. Ex vivo tropism of VSV-G was assessed using organotypic culture of explanted retina harvested from wild-type mice and human patients undergoing retinal detachment surgery to examine the prevention of transduction by physical barriers and species differences in tropism.

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Development of photoreceptor‐specific promoters and their utility to investigate EIAV lentiviral vector mediated gene transfer to photoreceptors

Abstract: It may be possible to use recombinant EIAV vectors containing photoreceptor-specific promoters to drive therapeutic gene expression to treat a range of retinal degenerative diseases where the photoreceptor cell is the primary disease target.

Cited by 20 publications

References 34 publications

Ocular gene delivery using lentiviral vectors

Ocular gene delivery using lentiviral vectors

Gene Therapy of Inherited Retinopathies: A Long and Successful Road from Viral Vectors to Patients

Vesicular Stomatitis Virus Glycoprotein– and Venezuelan Equine Encephalitis Virus-Derived Glycoprotein–Pseudotyped Lentivirus Vectors Differentially Transduce Corneal Endothelium, Trabecular Meshwork, and Human Photoreceptors

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