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Gene therapy for rare diseases

Gene therapies provide hope of a one-time treatment for numerous rare diseases that currently have no specific therapeutic options. Recent advances in genetic engineering and recombinant viral vector development have ignited interest in the field, with several gene therapy products gaining approval.  However, despite these successes, challenges in the field remain. This Collection explores recent improvements and applications of viral vector platforms for gene therapy delivery, with a focus on rare diseases.

In the first article, Gao and colleagues provide an overview of adeno-associated virus (AAV) vectors, discuss current trends and challenges in the field of AAV vector-mediated gene therapy and highlight key milestones that have enabled the transition of this platform to the bedside. In the second article, Cavazzana and colleagues assess the potential of using retroviral vectors for the genetic modification of haematopoietic stem and progenitor cells as an alternative to allogeneic transplantation in the treatment of rare inherited diseases, review clinical trial findings and address ongoing challenges in the field. In the final article, Tambuyzer and colleagues assess the respective strengths and limitations of the main therapeutic modalities — including gene therapy — as platforms for rare disease treatments, highlighting key characteristics, clinical successes and approvals.


Adeno-associated virus (AAV) vectors represent the leading platform for therapeutic gene delivery, with two recombinant AAV gene therapy products having gained regulatory approval in Europe or the United States. Here, Gao and colleagues discuss the fundamentals of AAV and vectorology, focusing on current therapeutic strategies, clinical progress and ongoing challenges.

Review Article | | Nature Reviews Drug Discovery

Advances in the design of vectors based on retroviruses, such as lentiviruses and gammaretroviruses, have led to improvements in the safety and stability of gene therapies directed at haematopoietic stem and progenitor cells. In this Review, Cavazzana and colleagues discuss the results from recent clinical trials of retroviral vectors for the treatment of genetic disorders, including severe combined immunodeficiencies and β-haemoglobinopathies (β-thalassaemia and sickle cell disease). They highlight the progress made and the remaining challenges in applying gene therapies more broadly.

Review Article | | Nature Reviews Drug Discovery

Most rare diseases still lack approved treatments. This article analyses the main therapeutic modalities available to researchers interested in translating advances in the scientific understanding of rare diseases into therapies, highlights progress so far and discusses overarching issues in drug development for rare diseases.

Review Article | | Nature Reviews Drug Discovery

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