Adeno-Associated Virus: A Promising Tool for Gene Delivery

2000 ◽  
pp. 155-181 ◽  
Author(s):  
A. M. Douar
Keyword(s):  
Gene Delivery ◽  
Adeno Associated Virus ◽  
Promising Tool

Recent advances in the analysis full/empty capsid ratio and genome integrity of adeno-associated virus (AAV) gene delivery vectors

2020 ◽  
Vol 20 ◽  
Author(s):  
L. Hajba ◽  
A. Guttman
Keyword(s):  
Gene Delivery ◽  
High Efficiency ◽  
Analytical Techniques ◽  
Viral Gene ◽  
Adeno Associated Virus ◽  
Gene Delivery Vectors ◽  
Empty Capsid ◽  
Purification Methods ◽  
Viral Gene Delivery

: Adeno-associated virus (AAV) is one of the most promising viral gene delivery vectors with long-term gene expression and disease correction featuring high efficiency and excellent safety in human clinical trials. During the production of AAV vectors,there are several quality control (QC)parameters that should be rigorously monitored to comply with clini-cal safety and efficacy. This review gives a short summary of the most frequently used AVV production and purification methods,focusing on the analytical techniques applied to determine the full/empty capsid ratio and the integrity of the encapsidated therapeutic DNA of the products.

scholarly journals Carbon Dot Nanoparticles: Exploring the Potential Use for Gene Delivery in Ophthalmic Diseases

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 935
Author(s):  
Manas R. Biswal ◽  
Sofia Bhatia
Keyword(s):  
Gene Delivery ◽  
Therapeutic Option ◽  
Retinal Dystrophy ◽  
Retinal Cells ◽  
Adeno Associated Virus ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Efficient Gene ◽  
New Type ◽  
Viral Nanoparticles

Ocular gene therapy offers significant potential for preventing retinal dystrophy in patients with inherited retinal dystrophies (IRD). Adeno-associated virus (AAV) based gene transfer is the most common and successful gene delivery approach to the eye. These days, many studies are using non-viral nanoparticles (NPs) as an alternative therapeutic option because of their unique properties and biocompatibility. Here, we discuss the potential of carbon dots (CDs), a new type of nanocarrier for gene delivery to the retinal cells. The unique physicochemical properties of CDs (such as optical, electronic, and catalytic) make them suitable for biosensing, imaging, drug, and gene delivery applications. Efficient gene delivery to the retinal cells using CDs depends on various factors, such as photoluminescence, quantum yield, biocompatibility, size, and shape. In this review, we focused on different approaches used to synthesize CDs, classify CDs, various pathways for the intake of gene-loaded carbon nanoparticles inside the cell, and multiple studies that worked on transferring nucleic acid in the eye using CDs.

scholarly journals Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles

2014 ◽  
Vol 194 ◽  
pp. 113-121 ◽  
Author(s):  
Kellie I. McConnell ◽  
Jessica Rhudy ◽  
Kenji Yokoi ◽  
Jianhua Gu ◽  
Aaron Mack ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Gene Delivery ◽  
Adeno Associated Virus

Abstract 247: Therapeutic Neovascularization by AAV2/9 Based Gene Transfer of hVEGF-A and hPDGF in Chronic Ischemia (rabbit model)

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Achim Pfosser ◽  
Chiraz El-Aouni ◽  
Franziska Globisch ◽  
Claudia Dinges ◽  
Andrea Fritz ◽  
...  
Keyword(s):  
Clinical Success ◽  
Rabbit Model ◽  
Capillary Density ◽  
Adeno Associated Virus ◽  
Promising Tool ◽  
Alkaline Phosphatase Staining ◽  
Collateral Growth ◽  
Anterior Tibial ◽  
Vessel Maturation ◽  
Long Acting

Therapeutic neovascularization by several growth factors is a concept well established in multiple animal models, albeit lacking clearcut clinical success to date. Therefore, we modified our therapeutic approach by combining the potent angiogenic agent hVEGF-A with hPDGF, a growth factor known for attracting pericytes and smooth muscle cells for arterial vessel maturation. In order to enhance efficacy, we utilized adeno-associated virus (AAV) 2/9, allowing for prolonged transgene expression. A lower hVEGF-AAV-concentration was used to avoid hemangiomaformation. 7 days after femoral artery excision, 1×10e11 hVEGF-A-AAV alone or in combination with 1×10e12 hPDGF-AAV particles were retroinfused into the anterior tibial vein of rabbits (n=5/group, p<0.05). LacZ-AAV2 was used as reporter-gene controls. At d7 and 35 angiography of both hindlimbs was performed for collateral quantification (% of d7 level) and frame count score (cinedensitometry, % of d7 level). Capillary density (Capillary muscle fiber ratio, CM/F) was assessed at d35 by PECAM-1 and alkaline-phosphatase-staining of the ischemic gastrocnemic and tibial anterior muscles, pericyte-quantification was assessed by NG2-staining. LacZ-expression was detected at d35 in control animals. hVEGF-A-AAV retroinfusion strongly induced angiogenesis (CM/F 1,32+0,07 vs. 0.96+0,08, controls), but failed to enhance collateral growth (125+7 vs. 95+6%, controls, p<0.05) or perfusion (frame count score: 136+12% vs. 107+9%, p=0.07). hVEGF-A/hPDGF co-application, however, enhanced perfusion (163+8%, p<0.05) via an increased collateral growth (146+9%, p<0.01) at a similar capillary density (1,44+0,10). We conclude, that efficacy of hVEGF-A-transfection is increased by hPDGF-co-transfection with a long-acting AAV. Utilizing this approach, the main target of hPDGF appears to be the collateral vasculature, complementary to the capillary growth induced by hVEGF-A. Thus, the combination of hVEGF-A and hPDGF combined with a long-acting AAV-vector is a promising tool in the quest of efficient therapeutic neovascularization.

scholarly journals Chemical modification of the adeno-associated virus capsid to improve gene delivery

2020 ◽  
Vol 11 (4) ◽  
pp. 1122-1131 ◽  
Author(s):  
Mathieu Mével ◽  
Mohammed Bouzelha ◽  
Aurélien Leray ◽  
Simon Pacouret ◽  
Mickael Guilbaud ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Chemical Modification ◽  
Neutralizing Antibodies ◽  
Cell Tropism ◽  
Amino Groups ◽  
Chemical Modifications ◽  
Virus Capsid ◽  
Adeno Associated Virus

Bioconjugated AAV vectors, achieved by coupling of ligands on amino groups of the capsid, are of great interest for gene delivery. Chemical modifications can be used to enhance cell tropism and to decrease interactions with neutralizing antibodies.

scholarly journals Adeno-Associated Virus (AAV) Capsid Stability and Liposome Remodeling During Endo/Lysosomal pH Trafficking

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 668 ◽  
Author(s):  
Bridget Lins-Austin ◽  
Saajan Patel ◽  
Mario Mietzsch ◽  
Dewey Brooke ◽  
Antonette Bennett ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Adeno Associated Virus ◽  
Lysosomal Ph ◽  
Negative Stain ◽  
Gene Delivery Vectors ◽  
Successful Infection ◽  
Monogenic Diseases ◽  
The Stability ◽  
Ssdna Viruses ◽  
Capsid Stability

Adeno-associated viruses (AAVs) are small, non-pathogenic ssDNA viruses being used as therapeutic gene delivery vectors for the treatment of a variety of monogenic diseases. An obstacle to successful gene delivery is inefficient capsid trafficking through the endo/lysosomal pathway. This study aimed to characterize the AAV capsid stability and dynamics associated with this process for a select number of AAV serotypes, AAV1, AAV2, AAV5, and AAV8, at pHs representative of the early and late endosome, and the lysosome (6.0, 5.5, and 4.0, respectively). All AAV serotypes displayed thermal melt temperatures that varied with pH. The stability of AAV1, AAV2, and AAV8 increased in response to acidic conditions and then decreased at pH 4.0. In contrast, AAV5 demonstrated a consistent decrease in thermostability in response to acidification. Negative-stain EM visualization of liposomes in the presence of capsids at pH 5.5 or when heat shocked showed induced remodeling consistent with the externalization of the PLA2 domain of VP1u. These observations provide clues to the AAV capsid dynamics that facilitate successful infection. Finally, transduction assays revealed a pH and temperature dependence with low acidity and temperatures > 4 °C as detrimental factors.

scholarly journals Targeted Gene Delivery into the Mammalian Inner Ear Using Synthetic Serotypes of Adeno-Associated Virus Vectors

2019 ◽  
Vol 13 ◽  
pp. 197-204 ◽  
Author(s):  
Min-A Kim ◽  
Nari Ryu ◽  
Hye-Min Kim ◽  
Ye-Ri Kim ◽  
Byeonghyeon Lee ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Inner Ear ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
Targeted Gene Delivery
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