title: Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy.
abstract: Despite significant advancements with recombinant AAV2 or AAV8 vectors for liver directed gene therapy in humans, it is well-recognized that host and vector-related immune challenges need to be overcome for long-term gene transfer. To overcome these limitations, alternate AAV serotypes (1-10) are being rigorously evaluated. AAV5 is the most divergent (55% similarity vs. other serotypes) and like AAV1 vector is known to transduce liver efficiently. AAV1 and AAV5 vectors are also immunologically distinct by virtue of their low seroprevalence and minimal cross reactivity against pre-existing AAV2 neutralizing antibodies. Here, we demonstrate that targeted bio-engineering of these vectors, augment their gene expression in murine hepatocytes in vivo (up to 16-fold). These studies demonstrate the feasibility of the use of these novel AAV1 and AAV5 vectors for potential gene therapy of diseases like hemophilia.
authors.affiliation: Department of Hematology, Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Dwaipayan
authors.initials: D
authors.lastname: Sen
authors.forename: Balaji
authors.initials: B
authors.lastname: Balakrishnan
authors.forename: Nishanth
authors.initials: N
authors.lastname: Gabriel
authors.forename: Prachi
authors.initials: P
authors.lastname: Agrawal
authors.forename: Vaani
authors.initials: V
authors.lastname: Roshini
authors.forename: Rekha
authors.initials: R
authors.lastname: Samuel
authors.forename: Alok
authors.initials: A
authors.lastname: Srivastava
authors.forename: Giridhara R
authors.initials: GR
authors.lastname: Jayandharan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D016466:CHO Cells; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics*; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry / Q000235:genetics; D013912:Threonine / Q000737:chemistry / Q000235:genetics; D014161:Transduction, Genetic; D054875:Ubiquitination
chemical_list: D057134:Antibodies, Neutralizing; D036022:Capsid Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013912:Threonine; D012694:Serine