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Ensuring a future for gene therapy for rare diseases

Hematopoietic stem-cell gene therapy has proven to be an effective treatment for several primary immunodeficiencies, and yet companies in this space are withdrawing from the EU market. Technological and regulatory innovations and a change to cost–benefit models are needed so that rare disease patients can receive these life-saving medicines.

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Fig. 1: Hematopoietic stem and progenitor cell gene therapy.


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Work in the labs of L.N. and A.A. is supported by grants from Fondazione Telethon, the EU Horizon 2020 Program, the Italian Ministry of Health, the Italian Ministry of University and Research, the Louis-Jeantet Foundation through the Jeantet-Collen Prize for Translational Medicine 2019 (to L.N.) and the Else Kröner Fresenius Foundation through the Kröner-Fresenius Prize for Medical Research 2020 (to A.A). The authors thank Michela Gabaldo, Aida Paniccia, Sara Maffioletti and Francesca Pampinella for helpful comments and support.

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Correspondence to Luigi Naldini.

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Competing interests

A.A. is PI of clinical trials sponsored by Orchard Therapeutics, which licensed gene therapy products for ADA-SCID, WAS, metachromatic leukodystrophy (MLD), β-thalassemia and mucopolysaccharidosis type I (MPS-I) originally developed at SR-Tiget. A.A. is a member of the Committee for Advanced Therapies (CAT) and his views are personal and may not be understood or quoted as being made on behalf of the European Medicines Agency (EMA). L.N. is an inventor on pending and issued patents on LV technology and gene editing filed by the Salk Institute, Cell Genesys, Telethon Foundation and/or San Raffaele Scientific Institute. L.N. is a founder of, owns equity in, and is a consultant and member of the scientific advisory board of Genenta Science, a biotechnology company aiming at developing cancer gene therapy by tumor-infiltrating monocytes, and Genespire, a biotechnology startup developing lentiviral-vector-based liver gene transfer and hematopoietic cell gene editing. F.P. has no competing interests.

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Aiuti, A., Pasinelli, F. & Naldini, L. Ensuring a future for gene therapy for rare diseases. Nat Med (2022).

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