Luigi Naldini

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Luigi Naldini (born 1959 in Turin) is an Italian gene therapist and professor of cell and tissue biology and of gene and cell therapy at Vita-Salute San Raffaele University in Milan. He is known as one of the pioneers of "development and applications of lentiviral vectors for gene transfer".[1]

Education and career[]

He graduated in 1983 with an M.D. from the University of Lecce and in 1987 with a Ph.D. in cell and tissue biology from the Sapienza University of Rome. His doctoral advisor was Paolo M. Comoglio. As a postdoc from 1987 to 1989, Naldini was supervised by Joseph Schlessinger in Rockville, Maryland. From 1990 to 1996 Naldini was an assistant professor in the University of Turin's department of biomedical sciences and oncology.[1] From 1994 to 1996 he was a visiting scientist at the Salk Institute in La Jolla, California,[1] where he worked in the laboratory of Inder Verma and Didier Trono; those two and Naldini jointly developed lentiviral vectors for gene transfer. From 1996 to 1998 Naldini worked in biotechnology in Foster City, California as a visiting scientist and director at Cell Genesys (which was taken over by BioSante Pharmaceuticals in 2009). From 1998 to 2002 he was an associate professor at the University of Turin's Medical School. At the Vita-Salute San Raffaele University's School of Medicine, he is since 2003 a full professor of cell and tissue biology. At Milan's San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), he was from 2003 to 2008 the co-director and is since 2008 the director.[1]

The demonstration of effective disease correction in animal models, coupled with the improved safety of the vector, moved lentiviral vectors to clinical testing, some of which were first performed in humans by Naldini and his team at SR-Tiget. Nearly one hundred patients suffering from rare fatal disorders such as X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Wiskott Aldrich syndrome and other severe combined immunodeficiencies, have been treated today with hematopoietic stem cells engineered with lentiviral vectors to replace the inherited defective gene. The vast majority of them were reported to be in good condition after 10 years and leading a normal or near-normal life, whereas they would probably have already succumbed to their disease if left untreated. More recently, this strategy has been applied to the treatment of beta-thalassemia.[2]

His research also advanced the "use of artificial nucleases for targeted genome editing in cell and gene therapy."[1]

As of 2021 Naldini's h-index was 117.[3] He is the author or co-author of over 275 articles.[1]

In 2008 Naldini was elected to the European Molecular Biology Organization (EMBO).[4] He was awarded in 2014 the Premio Gili Agostinelli of the  [it] (Academy of Sciences of Turin), in 2016 the Premio Lección Conmemorativa Jiménez Díaz, and in 2019 the Louis-Jeantet Prize for Medicine (in the special form of the Jeantet-Collen Prize for Translational Medicine).[2][5] He was the president of the European Society of Gene and Cell Therapy (ESGCT) and received an honorary doctorate from the Vrije Universiteit Brussel in 2015.[2] In 2017 he was honored with the American Society of Hematology's Ernest Beutler Lecture and Prize (jointly with Marina Cavazzana).[6]

Selected publications[]

  • Naldini, L.; Vigna, E.; Narsimhan, R. P.; Gaudino, G.; Zarnegar, R.; Michalopoulos, G. K.; Comoglio, P. M. (1991). "Hepatocyte growth factor (HGF) stimulates the tyrosine kinase activity of the receptor encoded by the proto-oncogene c-MET". Oncogene. 6 (4): 501–504. PMID 1827664.
  • Naldini, L.; Tamagnone, L.; Vigna, E.; Sachs, M.; Hartmann, G.; Birchmeier, W.; Daikuhara, Y.; Tsubouchi, H.; Blasi, F.; Comoglio, P.M. (1992). "Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/Scatter factor". The EMBO Journal. 11 (13): 4825–4833. doi:10.1002/j.1460-2075.1992.tb05588.x. PMC 556958. PMID 1334458.
  • Naldini, L.; Blomer, U.; Gage, F. H.; Trono, D.; Verma, I. M. (1996). "Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector". Proceedings of the National Academy of Sciences. 93 (21): 11382–11388. doi:10.1073/pnas.93.21.11382. PMC 38066. PMID 8876144.
  • Bussolino, F.; Di Renzo, M. F.; Ziche, M.; Bocchietto, E.; Olivero, M.; Naldini, L.; Gaudino, G.; Tamagnone, L.; Coffer, A.; Comoglio, P. M. (1992). "Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth". Journal of Cell Biology. 119 (3): 629–641. doi:10.1083/jcb.119.3.629. PMC 2289675. PMID 1383237.
  • Naldini, Luigi; Blömer, Ulrike; Gallay, Philippe; Ory, Daniel; Mulligan, Richard; Gage, Fred H.; Verma, Inder M.; Trono, Didier (1996). "In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector". Science. 272 (5259): 263–267. doi:10.1126/science.272.5259.263. PMID 8602510. S2CID 18997464.
  • Zufferey, Romain; Nagy, Dea; Mandel, Ron J.; Naldini, Luigi; Trono, Didier (1997). "Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo". Nature Biotechnology. 15 (9): 871–875. doi:10.1038/nbt0997-871. PMID 9306402. S2CID 6839921.
  • Blömer, U.; Naldini, L.; Kafri, T.; Trono, D.; Verma, I. M.; Gage, F. H. (1997). "Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector". Journal of Virology. 71 (9): 6641–6649. doi:10.1128/jvi.71.9.6641-6649.1997. PMC 191942. PMID 9261386.
  • Dull, Tom; Zufferey, Romain; Kelly, Michael; Mandel, R. J.; Nguyen, Minh; Trono, Didier; Naldini, Luigi (1998). "A Third-Generation Lentivirus Vector with a Conditional Packaging System". Journal of Virology. 72 (11): 8463–8471. doi:10.1128/JVI.72.11.8463-8471.1998. PMC 110254. PMID 9765382.
  • Zufferey, Romain; Dull, Thomas; Mandel, Ronald J.; Bukovsky, Anatoly; Quiroz, Dulce; Naldini, Luigi; Trono, Didier (1998). "Self-Inactivating Lentivirus Vector for Safe and Efficient in Vivo Gene Delivery". Journal of Virology. 72 (12): 9873–9880. doi:10.1128/JVI.72.12.9873-9880.1998. PMC 110499. PMID 9811723.
  • Follenzi, Antonia; Ailles, Laurie E.; Bakovic, Silvia; Geuna, Massimo; Naldini, Luigi (2000). "Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences". Nature Genetics. 25 (2): 217–222. doi:10.1038/76095. PMID 10835641. S2CID 6485634.
  • Verma, I. M.; Naldini, L.; Kafri, T.; Miyoshi, H.; Takahashi, M.; Blömer, U.; Somia, N.; Wang, L.; Gage, F. H. (2000). "Gene Therapy: Promises, Problems and Prospects". Genes and Resistance to Disease. pp. 147–157. doi:10.1007/978-3-642-56947-0_13. ISBN 978-3-642-63086-6.
  • Condorelli, G.; Borello, U.; De Angelis, L.; Latronico, M.; Sirabella, D.; Coletta, M.; Galli, R.; Balconi, G.; Follenzi, A.; Frati, G.; Cusella De Angelis, M. G.; Gioglio, L.; Amuchastegui, S.; Adorini, L.; Naldini, L.; Vescovi, A.; Dejana, E.; Cossu, G. (2001). "Cardiomyocytes induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration". Proceedings of the National Academy of Sciences. 98 (19): 10733–10738. doi:10.1073/pnas.191217898. PMC 58544. PMID 11535818.
  • Kay, Mark A.; Glorioso, Joseph C.; Naldini, Luigi (2001). "Viral vectors for gene therapy: The art of turning infectious agents into vehicles of therapeutics". Nature Medicine. 7: 33–40. doi:10.1038/83324. PMID 11135613. S2CID 15006207.
  • De Palma, Michele; Venneri, Mary Anna; Galli, Rossella; Sergi, Lucia Sergi; Politi, Letterio S.; Sampaolesi, Maurilio; Naldini, Luigi (2005). "Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors". Cancer Cell. 8 (3): 211–226. doi:10.1016/j.ccr.2005.08.002. PMID 16169466.
  • Brown, Brian D.; Venneri, Mary Anna; Zingale, Anna; Sergi, Lucia Sergi; Naldini, Luigi (2006). "Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer". Nature Medicine. 12 (5): 585–591. doi:10.1038/nm1398. PMID 16633348. S2CID 11114427.
  • Montini, Eugenio; Cesana, Daniela; Schmidt, Manfred; Sanvito, Francesca; Ponzoni, Maurilio; Bartholomae, Cynthia; Sergi, Lucia Sergi; Benedicenti, Fabrizio; Ambrosi, Alessandro; Di Serio, Clelia; Doglioni, Claudio; von Kalle, Christof; Naldini, Luigi (2006). "Hematopoietic stem cell gene transfer in a tumor-prone mouse model uncovers low genotoxicity of lentiviral vector integration". Nature Biotechnology. 24 (6): 687–696. doi:10.1038/nbt1216. PMID 16732270. S2CID 8966580.
  • Lombardo, Angelo; Genovese, Pietro; Beausejour, Christian M.; Colleoni, Silvia; Lee, Ya-Li; Kim, Kenneth A.; Ando, Dale; Urnov, Fyodor D.; Galli, Cesare; Gregory, Philip D.; Holmes, Michael C.; Naldini, Luigi (2007). "Gene editing in human stem cells using zinc finger nucleases and integrase-defective lentiviral vector delivery". Nature Biotechnology. 25 (11): 1298–1306. doi:10.1038/nbt1353. PMID 17965707. S2CID 16008349.
  • Mazzieri, Roberta; Pucci, Ferdinando; Moi, Davide; Zonari, Erika; Ranghetti, Anna; Berti, Alvise; Politi, Letterio S.; Gentner, Bernhard; Brown, Jeffrey L.; Naldini, Luigi; De Palma, Michele (2011). "Targeting the ANG2/TIE2 Axis Inhibits Tumor Growth and Metastasis by Impairing Angiogenesis and Disabling Rebounds of Proangiogenic Myeloid Cells". Cancer Cell. 19 (4): 512–526. doi:10.1016/j.ccr.2011.02.005. PMID 21481792.
  • Biffi, Alessandra; et al. (2013). "Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy". Science. 341 (6148). doi:10.1126/science.1233158. PMID 23845948. S2CID 206546808.
  • Naldini, Luigi (2015). "Gene therapy returns to centre stage". Nature. 526 (7573): 351–360. doi:10.1038/nature15818. PMID 26469046. S2CID 205246510.
  • Dull, Tom; Zufferey, Romain; Kelly, Michael; Mandel, R. J.; Nguyen, Minh; Trono, Didier; Naldini, Luigi (1998). "A Third-Generation Lentivirus Vector with a Conditional Packaging System". Journal of Virology. 72 (11): 8463–8471. doi:10.1128/JVI.72.11.8463-8471.1998. PMC 110254. PMID 9765382.
  • Zufferey, Romain; Dull, Thomas; Mandel, Ronald J.; Bukovsky, Anatoly; Quiroz, Dulce; Naldini, Luigi; Trono, Didier (1998). "Self-Inactivating Lentivirus Vector for Safe and Efficient in Vivo Gene Delivery". Journal of Virology. 72 (12): 9873–9880. doi:10.1128/JVI.72.12.9873-9880.1998. PMC 110499. PMID 9811723.

References[]

  1. ^ a b c d e f "Luigi Naldini". Università Vita-Salute San Raffaele (hsr.it).
  2. ^ a b c "Luigi Naldini. Winner of the 2019 Jeantet-Collen Prize for Translational Medicine". Louis-Jeantet Fondation.
  3. ^ "Luigi Naldini". Google Scholar.
  4. ^ "Luigi Naldini". embo.org. European Molecular Biology Organization.
  5. ^ "The Jeantet-Collen Prize for Translational Medicine". Fondation Louis-Jeantet.
  6. ^ "Ernest Beutler Lecture and Prize Recipients". American Society of Hematology.
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