Transformatx Update: Hematopoietic Stem Cell Gene Therapy Program

Quick Overview

Transformatx is providing an update on their lentiviral gene therapy program called ube-cel. The therapy involves taking stem cells from a patient, inserting a gene therapy vector, and then transplanting the cells back into the patient. The goal is to replace the nonfunctional copy of the gene and ensure the presence of working UBE3A in the brain. The therapy has shown promise in treating diseases such as metachromatic leukodystrophy. However, the use of certain promoters in gene therapy has raised concerns about the risk of cancer. Transformatx is now working on developing new vectors and optimizing the therapy to mitigate safety risks. Early-stage research is underway, and animal studies will be conducted to assess efficacy and safety before progressing to clinical trials.


Jennifer Panagoulias, Head of Regulatory and Policy for FAST, provides an update on the development of Transformatx’s lentiviral gene therapy program called ube-cel. This update was presented at the 2023 FAST Science Summit.

Background on Lentiviral Gene Therapy

Lentiviral gene therapy is an ex vivo approach to gene therapy, where the therapy is administered outside of the body. The goal is to replace the nonfunctional copy of a gene, in this case, UBE3A, and ensure its expression in the brain. Stem cells are taken from the patient and modified with the lentiviral vector containing the desired gene. These modified cells are then reintroduced into the patient’s body, where they differentiate into other blood cells and travel to the brain to express the gene.

Administration Process

The administration process for lentiviral gene therapy involves taking cells outside of the body. Stem cells are mobilized from the bone marrow through drug administration. These cells are then separated from the patient’s blood through a process called apheresis. The stem cells, specifically the CD34 cells, are modified with the gene therapy and prepared for transplantation back into the patient’s bone marrow. This process includes conditioning, where the patient undergoes a chemotherapeutic regimen to create space for the transplanted cells to engraft and grow.

Previous Successes and Challenges

Lentiviral gene therapy has been successfully used in the treatment of blood cancers and a CNS disorder called metachromatic leukodystrophy. The therapy has shown positive results in terms of gene expression and clinical benefits in patients.

However, challenges arose when a gene therapy called Skysona, which used a similar promoter to the one used in the lentiviral gene therapy for Angelman syndrome, was found to have a risk of cancer in patients. This prompted a closer examination of the safety concerns associated with the promoter used in gene therapies. The FDA approved both Skysona and another gene therapy called Zynteglo, but with different labeling reflecting the specific risks associated with each therapy.

Moving Forward

To mitigate the safety risks associated with the previous promoter, Transformatx partnered with a team at UCLA to explore different promoters and optimize the gene therapy sequence. In vitro studies have shown promising results, with the new vectors demonstrating good UBE3A expression and secretion.

The next steps involve animal studies to assess the efficacy, duration of effects, distribution in the brain, and safety of the new vectors. Regulatory meetings will also be conducted to pave the way for future clinical trials.


Transformatx’s lentiviral gene therapy program, ube-cel, shows promise in the treatment of Angelman syndrome. Ongoing research and development aim to further understand the safety and efficacy of the therapy, with the goal of advancing it to clinical trials in the future.

Talk details

  • Title: Transformatx Update: Hematopoietic Stem Cell Gene Therapy Program
  • Author(s): Jennifer Panagoulias
  • Author(s)’ affiliation: FAST
  • Publication date: 2023-11-12
  • Collection: 2023 FAST Science Summit