Gene therapy approaches to treat genetic immunodeficiencies
Our laboratory is studying the mechanisms by which an RNA virus is
maintained in resting B lymphocytes and how virus expression is controlled by
lymphocyte activators. We have showed in in vitro studies that viral
transcription, protein synthesis and replication are controlled by lymphocyte
activation. We are currently examining virus persistence in lymphocytes in vivo
and whether infectious virus can be reactivated after prolonged residence in B
lymphocytes. These observations will be used for the development of treatments
to control or clear acute and persistent infections.
Other studies in the lab focus on determining how developing B lymphocytes enter
and are maintained in the mature B cell pool in the periphery. Survival of
lymphocytes from normal mice are being compared to those which carry genetic
defects that alter B cell survival. Because of the need to transfer and express
genes in resting primary lymphocytes in these studies, we have developed a
transgenic mouse that expresses the receptor for adenovirus on lymphocytes. These
transgenic mice can be readily crossed with mice that carry genetic defects so
that we can use adenovirus, which efficiently infects and expresses engineered
genes in resting cells, to study gene function. These studies will be used to
develop new treatment modalities for use in gene therapy.
