“This is a review paper that summarizes recent progress in the field and, perhaps more importantly, describes the major intracellular barriers to gene delivery to help guide the design of new materials.”

Human gene therapy holds a tremendous potential for the treatment of many types of disease, ranging from cystic fibrosis to cardiovascular disease to cancer. A major limitation to reaching the clinic, however, is the need for gene delivery vectors that are both safe and efficient. The number of labs worldwide working toward the development of polymeric materials as nonviral vectors is very large and growing. Thus, the target audience for our review is large and highly active.

This is a review paper that summarizes recent progress in the field and, perhaps more importantly, describes the major intracellular barriers to gene delivery in order to help guide the design of new materials.

In gene therapy, one must introduce very large, fragile molecules of genetic material into the nucleus of specific cells in the body. Viruses are capable of efficient gene delivery, but have numerous disadvantages including safety concerns and high cost. As a result, many researchers are designing synthetic systems that can function as safe and inexpensive gene delivery vectors—i.e., artificial viruses. Our paper describes many of the important design criteria that must be considered in order to develop such synthetic vectors.

I began working on nonviral gene delivery vectors as a post-doctoral researcher in Robert Langer’s lab at MIT in 1996. The only real obstacle was that the field was (and is) relatively young and, as a result, there is a lot of uncharted territory.

Although many years of research will be required before it becomes commonplace, human gene therapy holds the potential to cure genetic diseases—cystic fibrosis, muscular dystrophy, and hemophilia, for example—that are currently intractable and often fatal. This potential will ensure that the development of gene delivery vectors remains a hot research area for the foreseeable future.