Evaluating the Impact of Natural IgM on Adenovirus Type 5 Gene Therapy Vectors

Zhili Xu1, Jie Tian1, Andrew W Harmon1

  • 1Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD, 20993, USA.

Natural IgM antibodies have an innate ability to recognize many viruses and viral-based gene therapy vectors. Naive mice have natural IgM antibodies that bind to adenoviruses, and these antibodies can profoundly affect the biodistribution and efficiency of gene delivery by adenovirus type 5 vectors. Here, we present protocols for isolating IgM from mouse serum, for assaying the concentration and adenoviral reactivity of mouse IgM, and for evaluating how natural antibodies and complement can synergize to neutralize adenovirus vectors.