[50] Cross-species comparison of in vivo reporter gene expression after recombinant adeno-associated virus-mediated retinal transduction

Bennett, Jean; Bhatt, Anand; Gm, Acland; Maguire, AM

doi:10.1016/s0076-6879(00)16762-x

Cited by 34 publications

(34 citation statements)

References 20 publications

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“…AAV serotype 2 (AAV2) has been used successfully and efficiently through subretinal injection to transduce photoreceptors and RPE in a number of gene therapy paradigms. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] This virus also targets ganglion cells efficiently if it is injected intravitreally 26,27 (Figure 1). AAV2 has not been found, as yet, to target structures in the anterior chamber of the eye.…”

Section: Discussionmentioning

confidence: 99%

“…After intraocular delivery of AAV, there is suppression of DTH, but an induction of IgG1 and IgG2b (Th2-type) antibodies. 26,27,49 This appears at least in part because of the fact that AAV does not transduce APCs. 48 This virus can, however, induce a strong antibody response directed at both viral antigens and the transgene.…”

Section: Immune Response To Intraocular Delivery Of Viral Vectors J Bmentioning

confidence: 99%

“…48 This virus can, however, induce a strong antibody response directed at both viral antigens and the transgene. [25][26][27] Antibodies are detected in intraocular fluid (anterior chamber fluid and vitreous) as well as in serum. Nevertheless, the immune response following intraocular injection of AAV is similar to that described in ACAID (ie, a predominant Th2 like response).…”

Section: Immune Response To Intraocular Delivery Of Viral Vectors J Bmentioning

confidence: 99%

“…Nevertheless, the immune response following intraocular injection of AAV is similar to that described in ACAID (ie, a predominant Th2 like response). [25][26][27]55 One question relating to the AAV-induced humoral response is whether it would be possible to readminister the virus/transgene in the presence of virus-specific antibodies. Studies in mice and in monkeys have demonstrated that these antibodies are not neutralizing and that it is possible to obtain additional transduction events.…”

Section: Immune Response To Intraocular Delivery Of Viral Vectors J Bmentioning

confidence: 99%

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Immune response following intraocular delivery of recombinant viral vectors

Bennett

2003

Gene Ther

116

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There has been significant progress in the last few years in demonstrating the utility of recombinant viral vectors in treating a variety of ocular diseases. The field has moved beyond 'proof-of-principle' and, in fact, has entered the phase where some of these vectors/paradigms are being or soon will be evaluated in human clinical trials. For this reason and also, to increase the understanding of immunological effects of transgenes/viral vectors on the eye, it is important to summarize what is known about these effects. Here, the biology of and immune responses to intraocular injection of three different recombinant viral vectors -adenovirus, adeno-associated virus (AAV), and lentivirus -are summarized. Perhaps, in part because of the unique immunological environment of the eye, the immunological effects of these viruses appear to be fairly benign. Nevertheless, a significant cell-mediated immune response can develop after intraocular administration of adenovirus. The magnitude of this response is affected by the nature of the intraocular compartment to which this virus is administered. Neither AAV nor lentivirus, however, elicit a cell-mediated response and are thus promising vectors for treatment of chronic ocular (retinal) diseases. Gene Therapy (2003) 10, 977-982.

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Section: Discussionmentioning

confidence: 99%

Section: Immune Response To Intraocular Delivery Of Viral Vectors J Bmentioning

confidence: 99%

Section: Immune Response To Intraocular Delivery Of Viral Vectors J Bmentioning

confidence: 99%

Section: Immune Response To Intraocular Delivery Of Viral Vectors J Bmentioning

confidence: 99%

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Immune response following intraocular delivery of recombinant viral vectors

Bennett

2003

Gene Ther

116

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“…[9][10][11][12][13] Furthermore, immunities to AAV capsids and/or transgene products represent a considerable barrier to efficient gene delivery by AAV and repeated administrations. 11,[14][15][16][17][18] Species and strains of animals, 14,19,20 routes of administration 16,17,21 and cellular localization of transgene products 22 are among the most important factors that influence the anti-AAV immunity and the subsequent outcome of AAV-mediated gene therapy. However, most studies have used a limited number of mouse strains and assessed the immune responses in a narrow fashion.…”

Section: Introductionmentioning

confidence: 99%