Luigi Naldini on His Lifelong Involvement with the Development of Gene Therapy.

Abstract

I joined the Salk to venture into the growing field of gene therapy. At that time I remember reading an editorial or interview by Harold Varmus about the problems of gene therapy, which were vectors, vectors, and vectors. This call to arms by Harold regarding vectors resonated with me and provided me with direction as to where to take my career. The key aspect was not enough efficiency. The Salk was a unique place for addressing that because of the combined expertise available. I joined the laboratory of Inder Verma, who had a lot of experience in developing gene therapies. Upstairs was a virology laboratory, where Didier Trono was working on HIV and discovering its unique ability to enter into the nucleus of infected non-dividing cells, a difference from other retroviruses. We applied the concept of exploiting HIV—and its unique capacity to infect cells and gain access to their nuclei—to make a more efficient vector. The other aspect of our research, once we had the vector built, was to prove that it was indeed more efficient. One important question was whether this vector would be able to transduce a non-dividing cell, which was the property we were trying to capture from HIV. The best model available at that Luigi Naldini, MD, PhD Director San Raffaele Telethon Institute for Gene Therapy Professor Cell and Tissue Biology and Gene Therapy School of Medicine Vita-Salute San Raffaele University Milan, Italy