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  1. Article: Evolution of dependoparvoviruses across geological timescales-implications for design of AAV-based gene therapy vectors.

    Hildebrandt, Evin / Penzes, Judit J / Gifford, Robert J / Agbandje-Mckenna, Mavis / Kotin, Robert M

    Virus evolution

    2020  Volume 6, Issue 2, Page(s) veaa043

    Abstract: Endogenous viral elements (EVEs) are genetic remnants of viruses that have integrated into host genomes millions of years ago and retained as heritable elements passed on to offspring until present-day. As a result, EVEs provide an opportunity to analyse ...

    Abstract Endogenous viral elements (EVEs) are genetic remnants of viruses that have integrated into host genomes millions of years ago and retained as heritable elements passed on to offspring until present-day. As a result, EVEs provide an opportunity to analyse the genomes of extinct viruses utilizing these genomic viral fossils to study evolution of viruses over large timescales. Analysis of sequences from near full-length EVEs of dependoparvoviral origin identified within three mammalian taxa, Whippomorpha (whales and hippos), Vespertilionidae (smooth-nosed bats), and Lagomorpha (rabbits, hares, and pikas), indicates that distinct ancestral dependoparvovirus species integrated into these host genomes approximately 77 to 23 million years ago. These ancestral viruses are unique relative to modern adeno-associated viruses (AAVs), and distinct from extant species of genus
    Language English
    Publishing date 2020-05-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/veaa043
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Prevalence of Adeno-Associated Virus 3 Capsid Binding and Neutralizing Antibodies in Healthy and Hemophilia B Individuals from India.

    Daniel, Hubert D-J / Kumar, Sanjay / Kannangai, Rajesh / Lakshmi, Kavitha M / Agbandje-Mckenna, Mavis / Coleman, Kirsten / Srivastava, Arun / Srivastava, Alok / Abraham, Asha Mary

    Human gene therapy

    2021  Volume 32, Issue 9-10, Page(s) 451–457

    Abstract: Adeno-associated virus (AAV) vector-based gene therapy offers a new treatment option for individuals with hemophilia. Pre-existing anti-AAV antibodies significantly impact the use of AAV vectors. Even relatively low titers of AAV neutralizing antibodies ( ...

    Abstract Adeno-associated virus (AAV) vector-based gene therapy offers a new treatment option for individuals with hemophilia. Pre-existing anti-AAV antibodies significantly impact the use of AAV vectors. Even relatively low titers of AAV neutralizing antibodies (NAb) from natural AAV infections against the capsid have been shown to inhibit the transduction of intravenously administered AAV in animal models and were associated with limited efficacy in human trials. This is important for determining the primary eligibility of patients for AAV vector-based gene therapy clinical trials. Current techniques to screen AAV antibodies include AAV capsid enzyme-linked immunosorbent assay (ELISA) for total antibodies and a transduction inhibition assay (TIA) for NAb. This study developed and screened total capsid binding anti-AAV3 antibodies by using ELISA and determined NAb levels by TIA using mCherry flow cytometry in healthy individuals with hemophilia B in India. One hundred and forty-three apparently healthy controls and 92 individuals with hemophilia B were screened. The prevalence of total and NAb in healthy controls was 79.7% and 65%, respectively; the prevalence of total and NAb in patients with hemophilia B for AAV3 was 92.4% and 91.3%, respectively.
    MeSH term(s) Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; Capsid ; Dependovirus/genetics ; Genetic Vectors/genetics ; Hemophilia B/genetics ; Hemophilia B/therapy ; Humans ; Prevalence
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2021-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1028152-6
    ISSN 1557-7422 ; 1043-0342
    ISSN (online) 1557-7422
    ISSN 1043-0342
    DOI 10.1089/hum.2020.258
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A myocardium tropic adeno-associated virus (AAV) evolved by DNA shuffling and in vivo selection

    Yang, Lin / Jiang, Jiangang / Drouin, Lauren M / Agbandje-Mckenna, Mavis / Chen, Chunlian / Qiao, Chunping / Pu, Dongqiuye / Hu, Xiaoyun / Wang, Da-Zhi / Li, Juan / Xiao, Xiao

    Proceedings of the National Academy of Sciences of the United States of America. 2009 Mar. 10, v. 106, no. 10

    2009  

    Abstract: To engineer gene vectors that target striated muscles after systemic delivery, we constructed a random library of adeno-associated virus (AAV) by shuffling the capsid genes of AAV serotypes 1 to 9, and screened for muscle-targeting capsids by direct in ... ...

    Abstract To engineer gene vectors that target striated muscles after systemic delivery, we constructed a random library of adeno-associated virus (AAV) by shuffling the capsid genes of AAV serotypes 1 to 9, and screened for muscle-targeting capsids by direct in vivo panning after tail vein injection in mice. After 2 rounds of in vivo selection, a capsid gene named M41 was retrieved mainly based on its high frequency in the muscle and low frequency in the liver. Structural analyses revealed that the AAVM41 capsid is a recombinant of AAV1, 6, 7, and 8 with a mosaic capsid surface and a conserved capsid interior. AAVM41 was then subjected to a side-by-side comparison to AAV9, the most robust AAV for systemic heart and muscle gene delivery; to AAV6, a parental AAV with strong muscle tropism. After i.v. delivery of reporter genes, AAVM41 was found more efficient than AAV6 in the heart and muscle, and was similar to AAV9 in the heart but weaker in the muscle. In fact, the myocardium showed the highest gene expression among all tissues tested in mice and hamsters after systemic AAVM41 delivery. However, gene transfer in non-muscle tissues, mainly the liver, was dramatically reduced. AAVM41 was further tested in a genetic cardiomyopathy hamster model and achieved efficient long-term δ-sarcoglycan gene expression and rescue of cardiac functions. Thus, direct in vivo panning of capsid libraries is a simple tool for the de-targeting and retargeting of viral vector tissue tropisms facilitated by acquisition of desirable sequences and properties.
    Keywords DNA shuffling ; animal models ; capsid ; cardiomyopathy ; caudal vein ; gene expression ; gene transfer ; hamsters ; liver ; mice ; muscles ; myocardium ; reporter genes ; serotypes ; tropisms ; viruses
    Language English
    Dates of publication 2009-0310
    Size p. 3946-3951.
    Publishing place National Academy of Sciences
    Document type Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0813207106
    Database NAL-Catalogue (AGRICOLA)

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