Genzyme Corporation

David Souza

Samuel C Wadsworth

Donna Armentano

Karen Vincent

Sirkka Kyostio-Moore

Provided herein are methods for producing an adeno-associated virus (AAV) particle containing an oversized recombinant AAV genome (e.g., greater than 4.7 kb). In some aspects, the invention provides AAV particles and AAV vectors comprising oversized rAAV genomes. Producer cell lines to produce AAV particles comprising oversized genomes are also provided.

Production of oversized adeno-associated vectors

The invention is directed to novel combinations of liver specific enhancers and promoter elements for achieving persistent transgene expression in the liver. The liver specific enhancer elements may be derived from either the human serum albumin, prothrombin, &#x3b1;-1microglobulin or aldolase genes in single copies or in multimerized form linked to elements derived from the cytomegalovirus intermediate early (CMV), &#x3b1;-1-antitrypsin or albumin promoters. In a preferred embodiment of the invention, an adenoviral vector comprising a liver specific enhancer/promoter combination operably linked to a transgene is administered to recipient cells. In other embodiments of the invention, adeno-associated viral vectors, retroviral vectors, lentiviral vectors or a plasmid comprising the liver specific enhancer/promoter combination linked to a transgene is administered to recipient cells. Also within the scope of the invention are promoter elements derived from the human prothrombin gene and the &#x3b2;-fibrinogen gene.

Growing community of inventors

Waltham, MA, United States of America

David Souza