Efficient Gene Transfer to Retinal Pigment Epithelium Cells With Long-Term Expression

Abstract

Second-generation FIV vectors can efficiently transfer genes into RPE cells with resulting long-term expression, properties potentially valuable to gene therapy approaches to some retinal diseases.

Ocular gene delivery using lentiviral vectors

“…For SIV, 26,28,29 and most studies involving HIV-1 vectors, 8,13,26,28,36,39,40,42,44,45 expression is restricted to these cells ( Figure 2). Additional transduction of neuroretinal neuronal and glial cells, albeit of variable efficiencies and distributions, is reported using HIV-1, (refs 16-18) HIV-2, (ref.…”

“…Additional transduction of neuroretinal neuronal and glial cells, albeit of variable efficiencies and distributions, is reported using HIV-1, (refs 16-18) HIV-2, (ref. 25) EIAV, (refs 30,33,35) BIV 35 and FIV 36,39,40,42 vectors in rodents, rabbits or NHPs, and by some groups delivering HIV-1 vectors in young rodents 7,10 (Figure 2). Lentiviral Typical transduction profiles of VSV-G-pseudotyped lentiviral vectors harbouring ubiquitous promoters after intraocular delivery in C57Bl/6J mice.…”

“…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.…”

Gene therapy progress and prospects: the eye

“…Human immunodeficiency virus-1 (HIV-1) and feline immunodeficiency virus (FIV)-based lentiviral vectors efficiently transduce the corneal endothelium and trabecular meshwork following delivery into the anterior chamber, 7,8 and stably transduce cells of the RPE for at least 2 years following delivery to the subretinal space in rodents. [8][9][10] Both HIV-1-based and simian lentiviral vectors are able to mediate therapeutic effects in RPE-based retinal degenerations. 10,11 Lentivirus-mediated transduction of photoreceptor cells appears to be less predictable than transduction of RPE cells, but is reported to occur under certain circumstances depending on retinal maturity, the promoter sequence used and anatomical barriers.…”

“…[12][13][14] The theoretical risk of recombination-mediated lentiviral replication may be minimized through the use of highly deleted vectors generated by re-coded packaging constructs in a four-plasmid system 15 and through the use of self-inactivating vectors. 16 Vectors based on nonprimate lentiviruses such as FIV, equine infectious anaemia virus and bovine immunodeficiency virus have transduction efficiencies and durations of expression in ocular tissues that are comparable to HIV-based vectors and may provide alternatives with potential safety advantages 8,9,15,16 (reviewed in detail elsewhere 17 ). The potential risk of lentivirus-mediated insertional mutagenesis is significantly lower in the eye than in systemic applications as the ocular cells targeted are relatively few in number and can be stably transduced by a proportionately low number of vector particles.…”