Research objectives and content
The project in general aims at the development of some novel anti-HIV strategies. In particular, the extreme codon bias that HIV exhibits will be exploited for the first time and appropriately engineered tRNAs will be used to induce multiple amino acid mutations to HIV proteins in HIV infected cells without affecting the cellular proteins.
In addition, a library of ribozymes targeted against several parts of the HIV genome will be generated and in vivo selection for optimal ribozymes will be carried out. These ribozymes will then be used in the context of HIV-based vectors, whose genes have been codon optimised, in order to provide a powerful anti-HIV gene therapy strategy. The use of HIV vectors has the advantages of targeting to HIV succeptible cells and of inhibition of viral spread as well. Furthermore, this strategy ensures efficient delivery of the vectors through the CD4+ population.
The above two strategies exploit the codon bias that HIV exhibits to produce some entirely novel anti-HIV therapeutics. This is the first time that this unusual feature of HIV has been exploited for therapeutic purposes. Furthermore, these studies could also add to our knowledge on HIV gene expression and replication.
Training content (objective, benefit and expected impact)
The training will include a great variety of modern molecular biology methods ( eg DNA manipulations, virus production and mammalian cell transduction, RT-PCR e.t.c. ). The benefits from it are expected to be many, since the field in which I will be trained is expected to become a major component of the biotechnology and pharmaceutical industries. The overall work is also expected to have a significant impact on gene therapy technology.
Links with industry / industrial relevance (22)
Gene therapy in general is a major component of the new biotechnology industry. Furthermore, the Kingsman laboratory have close links with a number of companies.