ex-vivo gene therapy
data set in the world.
our approach to gene therapy
bluebird bio is focused on gene addition. In gene addition therapies, functional copies of a gene are delivered to a patient’s stem cells using a delivery system called a “vector.” bluebird bio uses lentiviral vectors (LVVs) because they have unique properties that are well-suited to treating a range of severe genetic diseases.
Since each disease has a different underlying cause, we customize every gene therapy – through the design of the specific LVV used and manufacturing process – with the goal of addressing the respective cause of the various complex diseases we are aiming to treat.
LVV gene therapies are designed to be administered only once, and use different LVVs and manufacturing processes that are customized to allow a patient's body to produce the right protein where it is needed in the body.
LVV gene therapy has been deeply studied. In bluebird bio clinical trials, approximately 170 patients have been treated with investigational LVV gene therapies, with follow-up of up to seven years – which translates into more than 500 patient-years of experience.
The nature of LVV gene addition means these therapies are traceable, providing the ability to actively identify and track LVV-modified cells after delivery to a patient.
We have a knowledge base and tool set that allows experts to evaluate the potential role that gene therapy may have played in an adverse reaction.
Sophisticated and precise integration site analysis maps exactly where our LVVs integrate into the genome, enabling us to assess impact on DNA and monitor patients. With follow-up and tracking of LVV-modified cells for 15 years post-treatment with our investigational gene therapies in our clinical trials, we are driving the science in order to understand the safety – as well as the efficacy – of LVV gene therapy.
Through our robust research into LVVs to date, we have gained unique insights and applied these learnings to improve our clinical development programs.
We wouldn’t be here today without our ongoing collaboration with scientists, healthcare providers and most importantly, people with severe genetic diseases and their families and caregivers. Together, we are determined to build a brighter future for people living with severe genetic diseases.
Risk depends on the type of gene therapy, type of vector, and administration method. Some risks can be serious. Potential risks of gene therapy include:
- Insertional oncogenesis. The consequences of the insertion of genetic material can result in uncontrolled cell division that may lead to cancer, a known risk where DNA mutations can occur.
- Unintentional gene inactivation. With any type of gene therapy, there is the risk of unintentionally preventing the function of another important gene.
- A harmful immune reaction. An immune response to the gene therapy delivery system or the therapeutic protein could make the therapy less efficient. Risk of an immune response can be controlled by tailoring the viral dose to the patient.
- Administration process. There are different risks depending on whether gene therapy is directly administered to the cells in the body (in vivo) or if cells are genetically altered outside the body and transplanted back into the body (ex vivo). Ex vivo gene therapy and other technologies like gene editing require chemotherapy before administration. There are short and long term risks associated with chemotherapy, which can include anemia, cancer and infertility. Some of these risks may be managed through supportive care.
Gene therapy techniques are continually being researched. Patients, caregivers, and physicians should always discuss the risks and benefits of a specific gene therapy treatment.
Dunbar CE, High KA, Joung JK, Kohn DB, Ozawa K, Sadelain M. Gene therapy comes of age. Science. 2018;359(6372):eaan4672-eaan4672.
Negre O, Eggimann A-V, Beuzard Y, et al. Gene therapy of the β-hemoglobinopathies by lentiviral transfer of the βA(T87Q)-globin gene. Hum Gene Ther. 2016;27:148-165.
Morgan RA, Gray D, Lomova A, Kohn DB. Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned. Cell Stem Cell. 2017;21(5):574-590.
Goswami R, Subramanian G, Silayeva L, et al. Gene therapy leaves a vicious cycle. Front Oncol. 2019;9:297.
Bone Marrow & Cancer Foundation. Your Transplant Journey. Available at: https://bonemarrow.org/images/documents/Your-Transplant-Journey---Bone-Marrow--Cancer-Foundation.pdf. Accessed April 2022.
bluebird bio. Unpublished data on file.