APR 08, 2021 2:15 PM EDT

Functional Roles of the Novel Membrane-Associated AAV Protein MAAP

Speaker
  • Senior Scientist, Kuopio Center for Gene and Cell Therapy
    Biography

      Dr. Lionel Galibert has accumulated over 15 years of experience in the adeno-associated virus (AAV) gene therapy field. On the team of Dr. Otto Wilhelm Merten in Genethon, France, he helped develop a single baculovirus to produce rAAV8 in Sf9 cells, as well as demonstrated the involvement of the baculovirus protease on the degradation of certain AAV capsids. Dr. Galibert then worked within Dr. Michael Linden's group at Pfizer in London, and was involved in the development of the rAAV production system in fixed-bed bioreactors using mammalian cells. For the last 4 years, Dr. Galibert worked in Kuopio's biotech environment with positions in FinVector and its sister company Kuopio Center for Gene and Cell therapy. Now working in Dr. Kari Airenne's group, he leads their AAV research with a particular focus on the wild-type AAV. He will be presenting the work they performed on the novel AAV protein “Membrane-Associated Accessory Protein” MAAP.


    Abstract

    The adeno-associated virus (AAV) has evolved overlapping genes to maximize its genome use, as with the recently-discovered ORF in the cap gene which encodes a membrane-associated accessory protein (MAAP) located in the same genomic region as the VP1/2 unique domain. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. To study the role of MAAP in wild-type AAV (wt-AAV), we made point mutations along the MAAP ORF while keeping overlapping capsid proteins' ORFs intact. In cells co-transfected with plasmids encoding wt-AAV genome and adenovirus helper genes, MAAP localized in the plasma membrane, as well as intracellular membranes. Both inactivation and truncation of MAAP translation affected the emergence and intracellular distribution of the AAV capsid proteins. Importantly, while MAAP was beneficial for wt-AAV replication/infection, it was not essential for AAV generation. Oppositely, some MAAP-modifications resulted in substantially improved virus yields and capsid integrity. Altogether, our results reveal some MAAP functions having important implications for better-quality and quantity production of AAV vectors for therapeutic purposes.


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