Michele P. Calos
Non-viral vectors for gene therapy
Our current research is focused on development of novel vectors for gene therapy. We are creating non-viral vectors in order to avoid the safety problems and other limitations of viral vectors. Our main approach is to use extrachromosomal replicating vectors to carry the gene of interest. We are also interested in developing vectors that will integrate at specific sites in the genome.
Our extrachromosomal vectors are based on technology developed in the lab over the past several years. We isolated sequences from the human genome that can mediate autonomous replication. We paired these sequences with elements derived from Epstein-Barr virus that can mediate nuclear retention of the vectors in mammalian cells. Background information about these vectors can be found in the references listed below. In the Wolgemuth et al. 1996 study, we showed that gene expression from these vectors is greatly prolonged compared to expression from conventional plasmid vectors.
Non-viral DNA vectors can be delivered to various tissues using a growing variety of methods. We are attempting to deliver the vectors to mice using cationic liposomes, in collaboration with a local biotechnology company. Some diseases of immediate interest to us are cystic fibrosis, hemophilia, and cancer.