[47] Construction of encapsidated (gutted) adenovirus minichromosomes and their application to rescue of photoreceptor degeneration

Kumar‐Singh, Rajendra; Yamashita, Clyde K.; Tran, Ken; Farber, Débora B.

doi:10.1016/s0076-6879(00)16759-x

Cited by 13 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Viral purification was carried out using the adenopure purification kit (Puresyn Inc., Malvern, PA, USA) and viral titer determined at an optical density of 260 using a spectrophotometer, and then plaque purified as previously described. 7 The hCD46- and polyadenylation-, previously published 18 , expressing viruses are subsequently referred to as AdCAGCD46 and AdCAGpA, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…1,2 Recombinant adenovirus constructs have a significant tropism for retinal pigment epithelial (RPE) cells 3 and can persist in this tissue in rodents for at least 1 year (latest time point examined) 4 or potentially for the ‘lifetime’ of the animal. 5 In addition, helper-dependent adenovirus vectors can accommodate transgene expression cassettes up to 36 Kb, 6,7 allowing for the expression of multiple transgenes as well as the inclusion of native gene-regulatory elements.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration

2011

View full text Add to dashboard Cite

Activation of the alternative pathway of the complement system has been implicated in the pathogenesis of age-related macular degeneration. Membrane attack complex (MAC) has been identified mainly on the Bruch’s membrane and drusen underlying the retinal pigment epithelium (RPE). Membrane cofactor protein (CD46) preferentially regulates the alternative pathway of complement. The aim of this study was to evaluate the potential of increasing CD46 expression on RPE cells using an adenovirus as a gene therapy approach to reduce alternative pathway-mediated damage to RPE cells. We generated a recombinant adenovirus vector expressing human CD46 (hCD46) and delivered the vector to murine hepatocytes and RPE cells in vitro. After incubation in human serum in conditions in which the classical pathway of complement was blocked, we measured alternative pathway-mediated damage of these cells by quantifying lysis and MAC formation. Adenovirus expressing hCD46 was delivered to the subretinal space of adult mice, and 1 week later, ocular flat mounts were challenged with human serum and the levels of complement-mediated damage was quantified. Adenovirus-mediated delivery of hCD46 localizes to the basal and lateral surfaces of RPE cells where it offers protection from alternative pathway-mediated damage, but not classical, allowing the classical pathway to function unhindered.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration

2011

View full text Add to dashboard Cite

show abstract

“…38, 39), photoreceptor transduction can be enhanced. These modified vectors have been used with some success in animal models of primary photoreceptor disease such as STGD1 (lentivirus) or AR RP caused by PDE6B mutations (rAd) (40,41). Lentiviruses are integrating vectors and thus mediate stable transgene expression (assuming the appropriate promoter is used), although there is a risk of insertional mutagenesis (42).…”

Section: Figurementioning

confidence: 99%

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Hollander

Black²,

Bennett³

et al. 2010

J. Clin. Invest.

184

100

View full text Add to dashboard Cite

Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease-causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.

show abstract

“…To reduce immunogenicity, a gutted (or gutless) Ad vector was developed containing only the ITR required for replication and 5 -cis-acting Ad encapsulation signals necessary for packaging [52]. However, this vector is difficult to produce, requiring the use of helper virus to provide all the viral proteins in trans [32].…”

Section: Adenovirusesmentioning

confidence: 99%

Delivery Systems for Gene Transfer

Collins¹

2010

Genomics

View full text Add to dashboard Cite

[47] Construction of encapsidated (gutted) adenovirus minichromosomes and their application to rescue of photoreceptor degeneration

Cited by 13 publications

References 25 publications

Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration

Adenovirus-mediated delivery of CD46 attenuates the alternative complement pathway on RPE: implications for age-related macular degeneration

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Delivery Systems for Gene Transfer

Contact Info

Product

Resources

About