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aav

PROGEN offers a wide range of AAV antibodies in different quantities and formats, such as lyophilisate or supernatant. For test purposes, a selection of AAV antibodies are available as 10 µg lyophilized samples.


Target organs for AAV

The twelve serotypes of human Adeno-Associated Virus (AAV) require the help of other viruses (herpesvirus or adenovirus) to infect a variety of organs, causing only a very mild immune response in humans. AAV2 is the only mammalian DNA virus that is known to integrate in a specific site of the genome.


Literature to organ-specific AAV expression

  1. Xiao, W. et al. Gene therapy vectors based on adeno-associated virus type 1. J. Virol.73, 3994–4003 (1999).
  2. Manfredsson, F. P., Rising, A. C. & Mandel, R. J. AAV9: A potential blood-brain barrier buster. Molecular Therapy17, 403–405 (2009).
  3. Sen, D. et al. Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy. Sci. Rep.6, (2013).
  4. Zabner, J. et al. Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer. J. Virol.74, 3852–3858 (2000).
  5. Shen, S., Troupes, A. N., Pulicherla, N. & Asokan, A. Multiple Roles for Sialylated Glycans in Determining the Cardiopulmonary Tropism of Adeno-Associated Virus 4. J. Virol.87, 13206–13213 (2013).
  6. Ai, J. et al. Adeno-associated virus serotype rh.10 displays strong muscle tropism following intraperitoneal delivery. Sci. Rep.7, (2017).
  7. Cheng, B. et al. Development of optimized AAV3 serotype vectors: Mechanism of high-efficiency transduction of human liver cancer cells. Gene Ther.19, 375–384 (2012).
  8. Mingozzi, F. & High, K. A. Immune responses to AAV vectors: Overcoming barriers to successful gene therapy. Blood122, 23–36 (2013).
  9. Richter, M. et al. Adeno-associated virus vector transduction of vascular smooth muscle cells in vivo. Physiol. Genomics2, 117–27 (2000).
  10. Mori, S. et al. Tissue distribution of cynomolgus adeno-associated viruses AAV10, AAV11, and AAVcy.7 in naturally infected monkeys. Arch. Virol.153, 375–380 (2008).
  11. Guo, Y. et al. A Single Injection of Recombinant Adeno-Associated Virus into the Lumbar Cistern Delivers Transgene Expression Throughout the Whole Spinal Cord. Mol. Neurobiol. (2016).
  12. Schmidt, M. et al. Adeno-Associated Virus Type 12 (AAV12): a Novel AAV Serotype with Sialic Acid- and Heparan Sulfate Proteoglycan-Independent Transduction Activity. J. Virol.82, 1399–1406 (2008).

Immunochemical AAV studies

Anti-AAV virus particle antibodies are suitable for the characterization of different stages of adeno-associated virus (AAV) infection and are very useful for the analysis of the AAV capsid assembly. The antibodies specifically recognize conformational epitopes in assembled capsids of different AAV serotypes. Hence, they exclusively react with intact AAV particles.

Viral capsid protein antibodies (VP) exclusively recognize AAV capsid proteins and are useful for immunolocalization studies of AAV capsid formation, or immunoprecipitation and western blot analysis of viral capsid proteins.

Anti-AAV replicase antibodies (Rep) react with selected replicase (Rep) proteins in human AAV-infected cells. Applications include immunolocalization or immunoblotting studies to investigate the correlation between Rep expression and the course of an infection.

Neutralizing AAV antibodies in gene therapy research

AAV vectors are powerful tools in gene therapy research and development. Recombinant AAV vectors (rAAV) corresponding to the different viral serotypes have successfully been used as universal gene shuttles in human cells. Neutralizing AAV antibodies present in serum or plasma may block transduction with AAV vectors. In a prescreening step before vector administration, the titer of neutralizing AAV antibodies can be determined in a cell-based assay. PROGEN's AAV antibodies are ideal positive controls that neutralize wild-type AAV capsids of AAV serotypes 1, 2, 5, 6, 8, and 9.

PROGEN supplements its portfolio of AAV antibodies with advanced recombinant IgGs that feature optimal stability and batch-to-batch consistency. These antibodies retain equal performance compared to the mouse monoclonal antibodies with respect to cross-reactivity, AAV capsid recognition and binding sensitivity (see figure).





Publications with PROGEN´s AAV antibodies

  1.        Bennett, A. D. et al. AAV6 K531 serves a dual function in selective receptor and antibody ADK6 recognition. Virology 518, 369–376 (2018).
  2.        Wu, Y. et al. A Recombinant Baculovirus Efficiently Generates Recombinant Adeno-Associated Virus Vectors in Cultured Insect Cells and Larvae. Mol. Ther. Methods Clin. Dev. 10, 38–47 (2018).
  3.        Schiller, L. T., Lemus-Diaz, N., Rinaldi Ferreira, R., Böker, K. O. & Gruber, J. Enhanced Production of Exosome-Associated AAV by Overexpression of the Tetraspanin CD9. Mol. Ther. Methods Clin. Dev. 9, 278–287 (2018).
  4.        Tseng, Y.-S. et al. Generation and characterization of anti-Adeno-associated virus serotype 8 (AAV8) and anti-AAV9 monoclonal antibodies. J. Virol. Methods 236, 105–110 (2016).
  5.        Tseng, Y.-S. et al. Adeno-associated virus serotype 1 (AAV1)- and AAV5-antibody complex structures reveal evolutionary commonalities in parvovirus antigenic reactivity. J. Virol. 89, 1794–808 (2015).
  6.        Mietzsch, M. et al. OneBac: platform for scalable and high-titer production of adeno-associated virus serotype 1-12 vectors for gene therapy. Hum. Gene Ther. 25, 212–22 (2014).
  7.        Jin, L. F. et al. Ultrasound targeted microbubble destruction stimulates cellular endocytosis in facilitation of adeno-associated virus delivery. Int. J. Mol. Sci. 14, 9737–9750 (2013).
  8.        Naumer, M. et al. Properties of the Adeno-Associated Virus Assembly-Activating Protein. J. Virol. 86, 13038–13048 (2012).
  9.        Gurda, B. L. et al. Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8. J. Virol. 86, 7739–51 (2012).
  10.        Raupp, C. et al. The Threefold Protrusions of Adeno-Associated Virus Type 8 Are Involved in Cell Surface Targeting as Well as Postattachment Processing. J. Virol. 86, 9396–9408 (2012).
  11.        Varadi, K. et al. Novel random peptide libraries displayed on AAV serotype 9 for selection of endothelial cell-directed gene transfer vectors. Gene Ther. 19, 800–809 (2012).
  12.        Sonntag, F. et al. The Assembly-Activating Protein Promotes Capsid Assembly of Different Adeno-Associated Virus Serotypes?. J. Virol. 85, 12686–12697 (2011).
  13.        Fragkos, M., Breuleux, M., Clément, N. & Beard, P. Recombinant adeno-associated viral vectors are deficient in provoking a DNA damage response. J. Virol. 82, 7379–87 (2008).
  14.        Kuck, D., Kern, A. & Kleinschmidt, J. A. Development of AAV serotype-specific ELISAs using novel monoclonal antibodies. J. Virol. Methods 140, 17–24 (2007).
  15.        Grimm, D., Kay, M. A. & Kleinschmidt, J. A. Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. Mol. Ther. 7, 839–850 (2003).
  16.        Yan, Z. et al. Ubiquitination of both adeno-associated virus type 2 and 5 capsid proteins affects the transduction efficiency of recombinant vectors. J. Virol. 76, 2043–53 (2002).
  17.        Zhang, H.-G. et al. Addition of six-His-tagged peptide to the C terminus of adeno-associated virus VP3 does not affect viral tropism or production. J. Virol. 76, 12023–12031 (2002).
  18.        Wobus, C. E. et al. Monoclonal antibodies against the adeno-associated virus type 2 (AAV-2) capsid: epitope mapping and identification of capsid domains involved in AAV-2-cell interaction and neutralization of AAV-2 infection. J Virol 74, 9281–9293 (2000).
  19.        Moskalenko, M. et al. Epitope Mapping of Human Anti-Adeno-Associated Virus Type 2 Neutralizing Antibodies: Implications for Gene Therapy and Virus Structure. J. Virol. 74, 1761–1766 (2000).
  20.        Grimm, D. et al. Titration of AAV-2 particles via a novel capsid ELISA: packaging of genomes can limit production of recombinant AAV-2. Gene Ther. 6, 1322–1330 (1999).
  21.        Bartlett, J. S., Kleinschmidt, J., Boucher, R. C. & Samulski, R. J. Targeted adeno-associated virus vector transduction of nonpermissive cells mediated by a bispecific F(ab’gamma)2 antibody. Nat. Biotechnol. 17, 181–6 (1999).
  22.        Wistuba, A., Kern, A., Weger, S., Grimm, D. & Kleinschmidt, J. A. Subcellular compartmentalization of adeno-associated virus type 2 assembly. J. Virol. 71, 1341–52 (1997).