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Adeno-Associated Virus-Based Delivery Systems
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
The adeno-associated virus (AAV) has been the subject of intense study recently by investigators working with viral-based gene delivery systems. AAV is a member of the Dependovirus genus in the Parvoviridae family. Parvoviruses are small, single-stranded DNA viruses with a host range in both the vertebrates and invertebrates (1). AAV is often called a defective or dependent virus because it requires a helper virus to generate a productive infection. From 49% to 80% of human adults are seropositive for AAV type 2 (2-5). It has been speculated that AAV evolved from cellular “junk” DNA into a protective interfering transposon under evolutionary pressures which favored its transposonlike qualities (6). Transposons would interfere with invading pathogenic viruses (such as the parvovirus B19) by competing with the pathogen DNA for replicative enzymes. Thus the common ancestry for autonomous and defective parvoviruses may have been in cellular DNA which then developed under different evolutionary pressures to establish two genera. The features that make AAV an attractive potential gene therapy vector include nonpathogenicity, site-specific integration in the absence of a helper virus infection, and the ability to remove all of the viral genes without loss of infectivity.
What’s new and what’s next for gene therapy in Pompe disease?
Published in Expert Opinion on Biological Therapy, 2022
Angela L. Roger, Ronit Sethi, Meredith L. Huston, Evelyn Scarrow, Joy Bao-Dai, Elias Lai, Debolina D. Biswas, Léa El Haddad, Laura M. Strickland, Priya S. Kishnani, Mai K. ElMallah
Manuscripts for this systematic review were identified in the PubMed Database using the following search terms: (glycogen storage disease type II[MeSH Terms] AND genetic therapy[MeSH Terms]), (glycogen storage disease type II [MeSH Terms] AND dependovirus[MeSH Terms]), (glycogen storage disease type II [MeSH Terms] AND adenoviridae[MeSH Terms]), (glycogen storage disease type II [MeSH Terms] AND lentivirus[MeSH Terms]), and (glycogen storage disease type II [MeSH Terms] AND retroviridae[MeSH Terms]). Exclusion criteria were determined prior to reviewing the resulting manuscripts. Exclusion criteria included: non-English manuscripts, prior reviews, and not pertaining to the scope of the review (gene therapy for Pompe disease). Additional manuscripts within the scope of the review that did not result with our search terms were also included. Figure 1 shows the inclusion and exclusion of manuscripts from these findings.
A rAAV2/6 Mutant with Enhanced Targeting for Mouse Retinal Müller Cells
Published in Current Eye Research, 2020
Jinjing Cao, Xiaomei Liu, Yun Yuan, Feifei Wang, Wen Kong, Guohua Shi, Wensheng Li, Chun Zhang
Adeno-associated viruses are small, non-enveloped viruses belonging to the genus Dependovirus of the family Parvoviridae.1 Compared with other viral vectors, AAV has advantages in gene therapy, such as non-pathogenicity, low immunogenicity, and wide infection spectrum.2 AAV have been widely applied in gene therapy for various diseases. AAV has been used for tumor gene therapy. Expression of rAAV/Bevacizumab can inhibit tumor growth in vivo.3 AAV-mediated IFN-β and TRAIL can also increase the therapeutic function for tumors.2 AAV gene therapy is very successful for the treatment of hemophilia. Peripheral-vein infusion of scAAV2/8-LP1-hFIXco in patients with hemophilia B resulted in FIX transgene expression at levels sufficient to improve the bleeding phenotype, so as to achieve the purpose of AAV-mediated gene therapy for hemophilia B.4 Intravenous injection of AAV5-hFVIII-SQ in patients with hemophilia A is beneficial to maintain normal levels of factor VIII, so it is effective in treating hemophilia A.5 Gene therapy is demonstrated to be a good treatment strategy for Parkinson’s disease (PD). The use of AAV2-AADC could increase the production of dopamine in the striatum and achieve the goal of alleviating Parkinson’s disease.6 Overexpression of AAV-hαsyn in Syn III knockout mice demonstrates that Syn III can serve as a novel therapeutic target for PD.7
Delivering CRISPR: a review of the challenges and approaches
Published in Drug Delivery, 2018
Christopher A. Lino, Jason C. Harper, James P. Carney, Jerilyn A. Timlin
AAV, of the Dependovirus genus and Parvoviridae family, is a single stranded DNA virus that has been extensively utilized for gene therapy (Daya and Berns, 2008; Samulski and Muzyczka, 2014). AAV is an excellent vehicle for gene therapy for many reasons. AAV is not known to cause or relate with any diseases in humans. There is also a wide range of known serotypes which allow for infection of a multitude of cells with different specificities. The virus itself is able to efficiently infect cells while provoking little to no innate or adaptive immune response or associated toxicity, at least upon first treatment with a serotype (Daya and Berns, 2008). Immune responses are eventually seen to the capsid, sometimes even causing CD-8 T-cell toxicity (Samulski and Muzyczka, 2014). However, owing to the many serotypes of AAV with broad tropism, it is often possible to evade the problem of immune response to AAV should it arise. Finally, unlike some other methods, the use of AAV for gene therapy provides a persistent source of the provided DNA, as AAV-delivered genomic material can exist indefinitely in cells either as exogenous DNA or, with some modification, be directly integrated into the host DNA (Deyle and Russell, 2009). This can, of course, be either advantageous or disadvantageous depending on the desired goals of a specified modification. AAV particles can see application in in vitro, ex vivo, and in vivo work, making them highly versatile delivery vehicles.