Alternative adenovirus vector for gene therapy


The murine retroviruses and human adenoviruses are the two most frequently used viral vector systems The murine retrovirus system is versatile. Limitations: . Safety and no access to non dividing cells. The Ad5 vector can not efficiently transduce hematopoietic cells. Ad5 is pathogenic and persistent for several years in children. The prevalence of immunity against Ad5 is high. An anamnestic immune response is seen upon administration of Ad5 vector which impairs a sustained expression of the transgene.

Adenivirus Vectors for Haematopoietic Cells
Hematopoietic cells are attractive targets for gene-therapy. However, no satisfactory adenoviral vectors are currently available. A major problem with the most commonly used adenovirus (Ad) vectors, based on either Ad2 or Ad5, is their low binding efficiency for hematopoietic cells which do not express the coxackie adenovirus receptor (CAR). Ad2 and Ad5 and several other Ad serotypes use CAR as a primary attachment receptor. However, far from all adenoviruses uses CAR as a receptor. In our search for adenovirus serotypes that would make efficient vectors for hematopoietic cells we have identified two Ad serotypes, Ad11p and Ad35p, that binds very well to all kinds of hematopoietic cells. I have so far studied the interaction of these serotypes with different committed hematopoietic cell lines, i.e. their ability to bind and infect.


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PI: Göran Wadell