Phacilitate Lifetime Achievement Award 2024 For Advanced Therapies To Luigi Naldini

Luigi Naldini, director of San Raffaele Telethon Institute for Gene Therapy (SR-Tiget) and full professor of Histology and Gene and Cell Therapy at Vita-Salute San Raffaele University, received the lifetime achievement award Phacilitate Lifetime Achievement Award 2024 in recognition of his role as a pioneer in gene therapy and the impact of his research in the treatment of serious diseases, genetic and others. In particular, Prof. Naldini is credited with being the "father" of lentiviral vectors, therapeutic tools now widely used in the clinic and derived from one of the most feared human viruses, HIV.

The Phacilitate Advanced Therapies award recognizes innovations in the field of advanced therapies. Nominees were evaluated in two stages by a panel of international experts representing research institutions, universities, and the biotechnology industry. The award was established in 2023 and for the first time was presented to Carl June for the development of CAR-T cell therapy. The 2024 award ceremony was held on January 18^th in Miami, Florida, as a part of Advanced Therapies Week, with a broad scientific community in attendance.

"Prof. Naldini perfectly embodies the concept of an innovator. His unwavering dedication to developing therapies that benefit patients has driven him and his team not to be discouraged by early failures and to develop better and increasingly safe therapies. Without his dedication and perseverance, gene therapy would not be where it is today, able to change the lives of patients with drugs now approved for genetic diseases such as ADA-SCID and metachromatic leukodystrophy, not to mention the many others still in clinical development," says Sven Kili, chairman of the Phacilitate award jury.

After graduating in Medicine and Surgery and getting a doctorate in cytological and morphogenetic sciences in Turin, Italy, Prof. Luigi Naldini moved to the Salk Institute in La Jolla (USA), in the mid-1990s, where, working with Inder Verma and Didier Trono, he demonstrated the possibility of therapeutic gene transfer by exploiting the infectious characteristics of HIV and built the prototype lentiviral vectors in use worldwide today. After a stint in the San Francisco biotech world, where he further refined lentiviral vectors for safe clinical use, he returned to Italy (first in Turin and then in Milan). In 2008, he became director of SR-Tiget and continued the development of lentiviral technology by taking it to its first and effective clinical trials. As former president of the European Society for Gene and Cell Therapy (ESGCT) and a member of the European Molecular Biology Organization (EMBO), he has received major awards over the years, including the Outstanding Achievement Award from the American Society for Gene and Cell Therapy in 2014 and from ESGCT in 2015, the Jiménez Diaz Award in 2016, the Van Beutler Award from the American Society of Hematology in 2017, and the Jeantet-Collen Award for Translational Medicine in 2019. Prof. Naldini was also appointed to the Order of Merit of the Italian Republic in December 2019.

"I am grateful to my teachers, fantastic colleagues and excellent students who have accompanied me on this extraordinary journey from the laboratory to the hospital bed that has lasted nearly three decades, sharing their inspiration, difficulties and frustrations and, finally, successes. I also thank the members of the jury, who gave me this lifetime achievement award. I will continue to work with renewed energy and enthusiasm in the search for solutions based on gene and cell therapy for the many patients who need innovative therapies to deal with diseases hitherto considered fatal," Prof. Luigi Naldini commented at the award presentation.

His numerous awards demonstrate that Prof. Naldini has become a pivotal figure in the development of gene therapy and the application of lentiviral vectors for therapeutic gene transfer. These vectors, in addition to being among the most broadly utilized tools in the field of biomedical research, are already widely used in clinical settings. At Ospedale San Raffaele alone, nearly a hundred patients with serious genetic diseases, such as metachromatic leukodystrophy, Wiskott-Aldrich syndrome, beta thalassemia, and mucopolysaccharidosis type 1, have been treated using blood stem cells corrected by lentiviral vectors.

Overall, more than 400 people worldwide have received treatment based on blood stem cells engineered with lentiviral vectors, for 19 different diseases. A large proportion of these patients, who would otherwise have had little hope of survival in many cases, are now in good condition and living normal or at least significantly better lives. Four of these therapies have already received approval for market launch: among them is the gene medication for metachromatic leukodystrophy, which originated in the laboratories of the SR-TIGET Institute and has been a registered drug in the European Union since December 2020 and is also expected to be approved soon in the United States.

A large part of CAR-Ts undergoing clinical trials or already approved for commercial use in the world are also based on lentiviral vectors: these are gene therapy drugs aimed at fighting various types of blood or solid tissue cancers by selectively arming the patient's own killer lymphocytes against cancer cells. To date, more than 3,500 people are estimated to have benefited from this type of therapy.

Prof. Luigi Naldini's experimental research continues to come up with innovative solutions to expand the applications of gene therapy and further improve its efficacy and safety. In recent years, an anti-tumor gene therapy strategy has been developed based on the engineering of blood stem cells: the daughter cells generated from the stem cells, in particular monocytes, white blood cells, are able to effectively bring powerful signals to tumors that activate the immune response there, sparing the rest of the body from side effects. This strategy is still undergoing clinical trials at the Ospedale San Raffaele and Besta Hospitals in Milan for the treatment of glioblastoma, the most common and serious brain tumor in adults. The study is sponsored by Genenta Science, an innovative start-up founded by Prof. Naldini with Ospedale San Raffaele and now listed on Nasdaq.

In addition, Prof. Naldini's lab significantly contributed to the development of targeted gene editing, now conducted with CRISPR technology. These studies make it possible to rewrite the sequence of a gene, correcting its mutations rather than replacing its function with an additional version introduced with a vector, increasing the precision of genetic manipulation and paving the way for revolutionary new applications.