Agenda Details

Learn more about sessions and presentations at the 25th Annual Meeting

Detailed Program

Integrating Retroviral Vectors (Organized by the Education Committee)

Oncoretroviral vectors based upon the Moloney murine Leukemia virus (MoNMLV) were among the first to enter clinical trials testing gene transfer approaches to blood diseases. Though efficient gene transfer to hematopoietic stem cells, progenitors and mature blood elements became feasible in vitro, the need for cell division for transduction and integration limited efficiency when targeting engrafting hematopoietic stem cells (HSCs). Improved transduction methods led to the first successful application of gene transfer to HSCs, but this hope was soon overshadowed by the late occurrence of leukemia due to insertional mutagenesis attributed to MoMLV vector integration. Due in part to the ability to transduce both dividing and nondividing cells including HSCs, lentiviral vectors based upon HIV1 were developed. Pseudotyping with the VSV-G envelope allowed broad tropism and this vector system proved capable of carrying more complex payloads capable of driving high level, tissue specific expression of potentially therapeutic genes for diseases such as thalassemia and sickle cell disease. However, this progress was again met with the development of leukemia on a trial in sickle cell disease. In contrast, insertional mutagenesis was not implicated in the two cases described. In this session, we will hear about the development of these integrating vector systems, their use in clinical trials, and investigations into the most recent safety issues.

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