Adeno-associated virus-based vectors in gene therapy

Tal, Jacov

doi:10.1007/bf02253246

Cited by 48 publications

(22 citation statements)

References 160 publications

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“…Amazing progress in gene therapy and transfer products applied in clinical management of cancer, monogenic diseases, autoimmune diseases, HIV and bacterial infection. Viral delivery systems have been widely used in gene therapy protocols because of its high efficiency (19)(20)(21)(22). Gutless viral vector is safe with low oncogenicity, poor immunogenicity, and does not exaggerate the inflammatory reaction (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Protection of Immuno-Compromised Mice from Lethal Infection of Klebsiella Pneumonia by rAAV2-BPI23-Fcγ1 Gene Transfer

Kong

et al. 2008

Cell Mol Immunol

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Section: Discussionmentioning

confidence: 99%

Protection of Immuno-Compromised Mice from Lethal Infection of Klebsiella Pneumonia by rAAV2-BPI23-Fcγ1 Gene Transfer

Kong

et al. 2008

Cell Mol Immunol

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“…Vectors with up to 5.2 kb size can be packaged, although the optimal size for the AAV vector genome is between 4.1 and 4.9 kb. The rep and cap genes are provided in another plasmid, the package plasmid (Tal, 2000;Pfeifer and Verma, 2001). Acquisition of rAAV used to require the transfection of both constructs in Ad infected cells (Pfeifer and Verma, 2001).…”

Section: Aav-based Recombinant Vectorsmentioning

confidence: 99%

“…This minimizes the possibility of undesirable gene expression that causes host immune responses, as observed for other vectors. In addition to AAV capacity to infect both mitotic and post-mitotic cells, recent in vivo studies are resulting in efficient and persistent gene transfer to several tissues, organs and systems, including the central nervous system, retina, muscle, lung and liver (reviewed in Xiao and Samulski, 1998;Tal, 2000;Pfeifer and Verma, 2001). …”

Section: Aav-based Recombinant Vectorsmentioning

confidence: 99%

“…This suggests that proper regulation of AAV gene expression has a crucial role in rAAV production, and that the handling of the package plasmid to optimize gene expression can lead to an improvement in vector production. Moreover, the proper supply of helper functions from Ad essential genes is also crucial, since these genes regulate AAV gene expression and also modify the cellular microenvironment to allow AAV spreading (Tal, 2000;Pfeifer and Verma, 2001;Smith, 2003).…”

Section: Aav-based Recombinant Vectorsmentioning

confidence: 99%

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A role for adeno-associated viral vectors in gene therapy

Coura

Nardi

2008

Genet. Mol. Biol.

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Gene therapy constitutes a therapeutic intervention based on modification of the genetic material of living cells, by correcting genetic defects or overexpressing therapeutic proteins. The success of gene therapy protocols depends on the availability of therapeutically suitable genes, appropriate gene delivery systems and proof of safety and efficacy. Recent advances on the development of gene delivery systems, particularly on viral vectors engineering and improved gene regulatory systems, have led to marked progress in this field. Although the available vector systems can successfully transfer genes into cells, the ideal delivery vehicle has not been found. In this context, adeno-associated virus vectors (AAV) are arising as a promising tool for a wide range of applications, due to a combination of characteristics such as lack of pathogenicity and immunogenicity, wide range of cell tropism and long-term gene expression. Since its isolation, the biological properties of the adeno-associated virus have been increasingly understood, improving our ability to manipulate and use it as a safe and efficient gene therapy vector of wide spectrum. In this work, we review the bases of gene therapy, main types of gene transfer systems and basic properties and use of AAV vectors.

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“…Especially non-viral gene transfer benefits from biosafety and the unlimited gene size transportation capacity [9]. However, the major drawbacks of non-viral vectors are their poor in vivo transfection efficiencies resulting in low protein production, as well as their transient gene expression profile, which for improvement of local and temporal wound healing, is desirable.…”

Section: Introductionmentioning

confidence: 99%

The angiogenic response to PLL-g-PEG-mediated HIF-1α plasmid DNA delivery in healthy and diabetic rats

et al. 2013

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Impaired angiogenesis is a major clinical problem and affects wound healing especially in diabetic patients. Improving angiogenesis is a reasonable strategy to increase diabetes-impaired wound healing. Recently, our lab described a system of transient gene expression due to pegylated poly-l-lysine (PLL-g-PEG) polymer-mediated plasmid DNA delivery in vitro. Here we synthesized peptide-modified PLL-g-PEG polymers with two functionalities, characterized them in vitro and utilized them in vivo via a fibrin-based delivery matrix to induce dermal wound angiogenesis in diabetic rats. The two peptides were 1) a TG-peptide to covalently bind these nanocondensates to the fibrin matrix (TG-peptide) for a sustained release and 2) a polyR peptide to improve cellular uptake of these nanocondensates. In order to induce angiogenesis in vivo we condensed modified and non-modified polymers with plasmid DNA encoding a truncated form of the therapeutic candidate gene hypoxia-inducible transcription factor 1 (HIF-1 ). HIF-1 is the primarily oxygen-dependent regulated subunit of the heterodimeric transcription factor HIF-1, which controls angiogenesis among other physiological pathways. The truncated form of HIF-1 lacks the oxygen-dependent degradation domain (ODD) and therefore escapes degradation under normoxic conditions. PLL-g-PEG polymer-mediated HIF-1 -ΔODD plasmid DNA delivery was found to lead to a transiently induced gene expression of angiogenesis-related genes Acta2 and Pecam1 as well as the HIF-1 target gene Vegf in vivo. Furthermore, HIF-1 gene delivery was shown to enhance the number endothelial cells and smooth muscle cells -precursors for mature blood vessels -during wound healing. We show that -depending on the selection of the therapeutic target gene -PLL-g-PEG nanocondensates are a promising alternative to viral DNA delivery approaches, which might pose a risk to health. AbstractImpaired angiogenesis is a major clinical problem and affects wound healing especially in diabetic patients. Improving angiogenesis is a reasonable strategy to increase diabetes-impaired wound healing. Recently, our lab described a system of transient gene expression due to pegylated poly-L-lysine (PLL-g-PEG) polymermediated plasmid DNA delivery in vitro. Here we synthesized peptide-modified PLLg-PEG polymers with two functionalities, characterized them in vitro and utilized them in vivo via a fibrin-based delivery matrix to induce dermal wound angiogenesis in diabetic rats. The two peptides were 1) a TG-peptide to covalently bind these nanocondensates to the fibrin matrix (TG-peptide) for a sustained release and 2) a polyR peptide to improve cellular uptake of these nanocondensates. In order to induce angiogenesis in vivo we condensed modified and non-modified polymers with plasmid DNA encoding a truncated form of the therapeutic candidate gene hypoxiainducible transcription factor 1α (HIF-1α). HIF-1α is the primarily oxygen-dependent regulated subunit of the hetero-dimeric transcription factor HIF-1, which controls angiogenesis...

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Adeno-associated virus-based vectors in gene therapy

Cited by 48 publications

References 160 publications

Protection of Immuno-Compromised Mice from Lethal Infection of Klebsiella Pneumonia by rAAV2-BPI23-Fcγ1 Gene Transfer

Protection of Immuno-Compromised Mice from Lethal Infection of Klebsiella Pneumonia by rAAV2-BPI23-Fcγ1 Gene Transfer

A role for adeno-associated viral vectors in gene therapy

The angiogenic response to PLL-g-PEG-mediated HIF-1α plasmid DNA delivery in healthy and diabetic rats

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