Adeno-Associated Virus (AAV) as a Vector for Gene Therapy

Naso, Michael F.; Tomkowicz, Brian; Perry, William L.; Strohl, William R.

doi:10.1007/s40259-017-0234-5

Cited by 906 publications

(730 citation statements)

References 152 publications

Supporting

Mentioning

676

Contrasting

Unclassified

Order By: Relevance

“…A number of late‐stage clinical trials using viral vectors to treat diseases including retinal dystrophy, spinal muscular atrophy, and to X‐linked adrenoleukodystrophy are also in the pipeline 29. While this exciting development is realizing the potential of gene therapy, particularly for one‐time administration, chronic applications may still require nonviral gene vectors to deliver.…”

Section: Discussionmentioning

confidence: 99%

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

et al. 2018

View full text Add to dashboard Cite

Efficient nonviral oral gene delivery offers an attractive modality for chronic protein replacement therapy. Herein, the oral delivery of insulin gene is reported by a nonviral vector comprising a copolymer with a high degree of substitution of branched polyethylenimine on chitosan (CS‐g‐bPEI). Protecting the plasmid from gastric acidic degradation and facilitating transport across the gut epithelium, the CS‐g‐bPEI/insulin plasmid DNA nanoparticles (NPs) can achieve systemic transgene expression for days. A single dose of orally administered NPs (600 µg plasmid insulin (pINS)) to diabetic mice can protect the animals from hyperglycemia for more than 10 d. Three repeated administrations spaced over a 10 d interval produce similar glucose‐lowering results with no hepatotoxicity detected. Positron‐emission‐tomography and computed‐tomography images also confirm the glucose utilization by muscle cells. While this work suggests the feasibility of basal therapy for diabetes mellitus, its significance lies in the demonstration of a nonviral oral gene delivery system that can impact chronic protein replacement therapy and DNA vaccination.

show abstract

Section: Discussionmentioning

confidence: 99%

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For this virus to enter the lytic cycle, the presence of a herpes virus or an adenovirus is necessary to provide the proteins required for virus packaging. Because these viruses transfer genetic materials for therapeutic purposes with maximum efficiency and minimum triggering of the immune response compared to non‐viral and physical methods, they have recently become a significant subject of interest for researchers in the field of gene therapy . The expression of CRISPR/Cas9 system components by AAV viral vectors, as a model for homologous recombination, leads to a significant increase in the precision of in vivo genome editing.…”

Section: Introductionmentioning

confidence: 99%

“…To resolve the issue of pathogenicity in human cell lines as a result of AAVs, a variant was created via genetic engineering called the rAAV, which operates based on endogenous homologous recombination. rAAVs are technically nanoparticles with a protein‐based nature free of any viral DNA, which, by passing through the cell membrane and delivering the DNA of interest, apply a desired genomic alteration, such as DNA insertion, deletion or replacement, in the cells of a patient with high efficiency and a reduced number of off‐target recombination events …”

Section: Introductionmentioning

confidence: 99%

Creating cell and animal models of human disease by genome editing using CRISPR/Cas9

Zarei

Razban

Hosseini

et al. 2019

The Journal of Gene Medicine

View full text Add to dashboard Cite

A set of unique sequences in bacterial genomes, responsible for protecting bacteria against bacteriophages, has recently been used for the genetic manipulation of specific points in the genome. These systems consist of one RNA component and one enzyme component, known as CRISPR (“clustered regularly interspaced short palindromic repeats”) and Cas9, respectively. The present review focuses on the applications of CRISPR/Cas9 technology in the development of cellular and animal models of human disease. Making a desired genetic alteration depends on the design of RNA molecules that guide endonucleases to a favorable genomic location. With the discovery of CRISPR/Cas9 technology, researchers are able to achieve higher levels of accuracy because of its advantages over alternative methods for editing genome, including a simple design, a high targeting efficiency and the ability to create simultaneous alterations in multiple sequences. These factors allow the researchers to apply this technology to creating cellular and animal models of human diseases by knock‐in, knock‐out and Indel mutation strategies, such as for Huntington's disease, cardiovascular disorders and cancers. Optimized CRISPR/Cas9 technology will facilitate access to valuable novel cellular and animal genetic models with respect to the development of innovative drug discovery and gene therapy.

show abstract

“…The ability to produce high‐quality AAV vectors in large quantities is a major bottleneck for the development of gene therapy‐based medicine. In this respect, various manufacturing platforms for AAV vectors have been established . On the one hand, one major method currently employed for large scale AAV vector production is an insect cell line‐based platform using baculovirus infection .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of life cycle defective adenovirus mutants for production of adeno‐associated virus vectors

Krüger-Haag

Lehmann

Schmidt

et al. 2019

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background Adeno‐associated virus‐based vectors are efficient and safe drug candidates for different in vivo gene therapy applications. With increasing numbers of clinical studies based on AAV2 vectors that include not only rare, but also common diseases as a therapeutic target, there is an increased demand for the development of improved production technologies. Methods In the present study, we compared two life cycle defective adenovirus mutants as helper viruses for AAV2 vector production. They had deletions either in the gene coding for the preterminal protein (pTP) that is expressed early in the viral life cycle and is essential for genome replication or in the gene coding for the 100K protein, a protein with many functions, one of which is involved in virus assembly. AAV2 vector production efficiencies were evaluated by analyzing genome‐containing particles using a real‐time polymerase chain reaction and functional units were investigated by transduction assays. Results Somewhat contrary to our expectations, the ∆100K mutant virus showed only a moderate efficiency as a helper virus for AAV2 vector production, whereas the replication‐deficient ∆pTP mutant supported AAV2 production almost as efficiently as adenovirus wild‐type. We also showed that a temperature shift to 32°C together with extended incubation times improved AAV2 vector productivity. Conclusions The present study indicates the advantages of using a ∆pTP mutant adenovirus rather than adenovirus wild‐type as a helper virus for AAV2 production and also indicates that temperature shifts to lower temperatures may improve AAV2 vector production rates.

show abstract

Adeno-Associated Virus (AAV) as a Vector for Gene Therapy

Cited by 906 publications

References 152 publications

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

Creating cell and animal models of human disease by genome editing using CRISPR/Cas9

Evaluation of life cycle defective adenovirus mutants for production of adeno‐associated virus vectors

Contact Info

Product

Resources

About