Specific adeno-associated virus serotypes facilitate efficient gene transfer into human and non-human primate mesenchymal stromal cells

Purpose The most common virus vector used in gene therapy research for ophthalmologic diseases is the adeno-associated virus (AAV) vector, which has been used successfully in a number of preclinical and clinical studies. It is important to evaluate novel AAV vectors in animal models for application of clinical gene therapy. The AAV-DJ (type 2/type 8/type 9 chimera) was engineered from shuffling eight different wild-type native viruses. In this study, we investigated the efficiency of gene transfer by AAV-DJ injections into the retina. Methods One microliter of AAV-2-CAGGS-EGFP or AAV-DJ-CAGGS-EGFP vector at a titer of 1.4 × 10e12 vg/ml was injected intravitreally or subretinally in each eye of C57BL/6 mice. We evaluated the transduction characteristics of AAV-2 and -DJ vectors using fluorescence microscopy and electroretinography. Results The results confirmed that AAV-DJ could deeply transfer gene to photoreceptor layer with intravitreal injection and has an efficient gene transfer to various cell types especially the Mueller cells in the retina. Retinal function was not affected by AAV-DJ infection or ectopic EGFP expression. Conclusions The AAV-DJ vector efficiently induces the reporter gene in both the inner and outer murine retina without functional toxicity. These data indicated that the AAV-DJ vector is a useful tool for the gene therapy research targeting retinal disorders.

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Efficient gene transfer into the chick brain using avian adeno-associated virus vector

Neuroscience Research ◽

10.1016/j.neures.2011.07.1800 ◽

2011 ◽

Vol 71 ◽

pp. e410-e411

Author(s):

Ryosuke Matsui ◽

Dai Watanabe

Keyword(s):

Gene Transfer ◽

Virus Vector ◽

Chick Brain ◽

Adeno Associated Virus ◽

Efficient Gene

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Efficient Gene Transfer of HIV-1-Specific Short Hairpin RNA into Human Lymphocytic Cells Using Recombinant Adeno-associated Virus Vectors

Molecular Therapy ◽

10.1016/j.ymthe.2003.11.025 ◽

2004 ◽

Vol 9 (3) ◽

pp. 396-402 ◽

Cited By ~ 33

Author(s):

Daniel Boden ◽

Oliver Pusch ◽

Fred Lee ◽

Lynne Tucker ◽

Bharat Ramratnam

Keyword(s):

Gene Transfer ◽

Short Hairpin Rna ◽

Hairpin Rna ◽

Adeno Associated Virus ◽

Virus Vectors ◽

Efficient Gene ◽

Short Hairpin ◽

Hiv 1

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Remodeling of Human Osteochondral Defects via rAAV-Mediated Co-Overexpression of TGF-β and IGF-I from Implanted Human Bone Marrow-Derived Mesenchymal Stromal Cells

Journal of Clinical Medicine ◽

10.3390/jcm8091326 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1326

Author(s):

Stephanie Morscheid ◽

Jagadeesh Kumar Venkatesan ◽

Ana Rey-Rico ◽

Gertrud Schmitt ◽

Magali Cucchiarini

Keyword(s):

Bone Marrow ◽

Growth Factor ◽

Gene Transfer ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Human Model ◽

Cartilage Lesions ◽

Igf I

The application of chondrogenic gene sequences to human bone marrow-derived mesenchymal stromal cells (hMSCs) is an attractive strategy to activate the reparative activities of these cells as a means to enhance the processes of cartilage repair using indirect cell transplantation procedures that may improve the repopulation of cartilage lesions. In the present study, we examined the feasibility of co-delivering the highly competent transforming growth factor beta (TGF-β) with the insulin-like growth factor I (IGF-I) in hMSCs via recombinant adeno-associated virus (rAAV) vector-mediated gene transfer prior to implantation in a human model of osteochondral defect (OCD) ex vivo that provides a microenvironment similar to that of focal cartilage lesions. The successful co-overexpression of rAAV TGF-β/IGF-I in implanted hMSCs promoted the durable remodeling of tissue injury in human OCDs over a prolonged period of time (21 days) relative to individual gene transfer and the control (reporter lacZ gene) treatment, with enhanced levels of cell proliferation and matrix deposition (proteoglycans, type-II collagen) both in the lesions and at a distance, while hypertrophic, osteogenic, and catabolic processes could be advantageously delayed. These findings demonstrate the value of indirect, progenitor cell-based combined rAAV gene therapy to treat human focal cartilage defects in a natural environment as a basis for future clinical applications.

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