Alexion Pharmaceuticals, Inc.

William L Fodor

Scott A Rollins

Stephen P Squinto

Russell P Rother

Jeremy P Springhorn

Methods and compositions are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The reduction of levels of galactose alpha (1,3) galactosyl epitopes on the retroviral vector particles and/or the blockade of antibody binding to such epitopes have been found to render the particles less sensitive to inactivation by complement mediated mechanisms, and to thus allow transduction in the presence of complement containing body fluids. Means are provided for obtaining such reductions.

Methods and compositions for protecting retroviral vector particles and

Chimeric complement inhibitor proteins are provided which include a first functional domain (first amino acid sequence) having C3 inhibitory activity and a second functional domain (second amino acid sequence) having C5b-9 inhibitory activity. The first functional domain is amino terminal to the second functional domain. In this way, the chimeric protein exhibits both C3 and C5b-9 inhibitory activity. The other orientation, i.e., the orientation in which the second amino acid sequence is amino terminal to the first amino acid sequence, only produces C3 inhibitory activity. Nucleic acid molecules encoding such proteins are also provided.

Growing community of inventors

New Haven, CT, United States of America

William L Fodor