• Indian scientists have developed a groundbreaking gene therapy for severe Haemophilia A using lentiviral vectors.
• The therapy, developed by the Centre for Stem Cell Research, has shown transformational results in all five enrolled participants.
• The use of lentiviral vectors in gene therapy is a recent development, ideal for treating diseases requiring lifelong treatment.
• Despite the success, challenges related to safety, efficacy, and affordability of gene therapies remain.

Gene therapy, a groundbreaking medical approach, has been making significant strides in recent years. This innovative treatment method involves the introduction, removal, or alteration of genetic material within a patient's cells to treat or prevent disease. The primary source of information for this article focuses on a groundbreaking development in gene therapy for Haemophilia A, a severe bleeding disorder caused by the deficiency of clotting Factor VIII.

Indian scientists have developed the first-in-human gene therapy using lentiviral vectors for severe haemophilia A. The therapy was developed by the Centre for Stem Cell Research (CSCR) at Christian Medical College (CMC), Vellore, and supported by the Department of Biotechnology. The therapy has shown transformational results, with the successful production of zero annualised bleeding rates in all five enrolled participants while enabling prolonged production of Factor VIII, eliminating the need for repeated infusions.

This effect was observed over a cumulative follow-up of 81 months, correlating Factor VIII activity with vector copy numbers in the peripheral blood. The new gene therapy approach involves the use of a lentiviral vector to introduce a normal copy of the Factor VIII gene into autologous haematopoietic stem cells (HSCs). These modified HSCs generate blood cells capable of producing functional Factor VIII over extended periods.

The Journey of Gene Therapy

The development of gene therapy has been a long and complex journey. The concept of gene therapy was first proposed in the 1970s, but it took several decades of research and development before the first gene therapy trials were conducted in the 1990s. Early gene therapy trials faced numerous challenges, including issues with vector design, delivery methods, and immune responses. However, advancements in technology and a better understanding of human genetics have led to significant improvements in gene therapy techniques.

The use of lentiviral vectors in gene therapy is a relatively recent development. Lentiviruses are a type of retrovirus that can integrate their genetic material into the host cell's genome. This allows for long-term expression of the therapeutic gene, making them an ideal choice for treating diseases that require lifelong treatment, such as haemophilia A.

Gene Therapy: A Ray of Hope for Genetic Disorders

The success of the gene therapy for haemophilia A is a significant milestone in the field of gene therapy. It demonstrates the potential of gene therapy to provide a long-term solution for patients with severe genetic disorders. However, the journey to bring gene therapies to patients is far from over. There are still many challenges to overcome, including issues related to safety, efficacy, and affordability.

In addition to haemophilia A, gene therapy is also being explored for the treatment of other genetic disorders. For instance, gene therapy has shown promise in the treatment of Mucopolysaccharidosis type I, a rare genetic disorder caused by a deficiency of the enzyme IDUA. Researchers have successfully used genome editing techniques to correct the genetic defect in human hematopoietic stem cells, leading to the phenotypic correction of the disease.