Gene therapy

The three most efficient and popular gene-delivery vectors that can stably (permanently) integrate transgenes into host cell genomes are gamma-retroviruses, lentiviruses, and transposons. The major safety concern with the use of these integrated gene delivery systems is that they can cause insertional oncogenesis which can lead to host cell transformation and can lead to the development of cancer. 

All three integrative vectors: g-retroviruses, lentiviruses, and transposons integrate large amounts of backbone DNA into host cells along with the desired transgene. Therefore, insertional oncogenesis is a concern with each. 

To decrease the risk of vector-induced host cell transformation, we and our colleagues at the University of South Alabama developed an innovative gene delivery vector, a minimal piggyBac transposon, which, using a single-plasmid system, can stably integrate transgenes into target cell genomes while delivering a significantly smaller amount of non-essential, potentially oncogenic, DNA than other integrative vectors such as retroviruses or full-length transposons. We did this by moving most of the terminal domains (with their potentially oncogenic-inducing enhancer/promoter sequences) to the helper part of the plasmid. The helper part of the plasmid is required for the successful integration of the transgene into the host cell genome, but is not itself integrated into the host cell’s genome. 

Currently, CompoVax is developing technology that can direct the minimal piggyBac to specific sites within the host cell genome using a guide RNA similar to that used in the CRISPR-Cas9 system. 

* Solodushko V, Bitko V, Fouty B. Minimal piggyBac vectors for chromatin integration. Gene Ther. 2014;21(1):1-9.

* Troyanovsky B, Bitko V, Fouty B, Solodushko V. Simple viral/minimal piggyBac hybrid vectors for stable production of self-inactivating gamma-retroviruses. BMC Res Notes. 2015;8:379.

* Troyanovsky B, Bitko V, Pastukh V, Fouty B, Solodushko V. The Functionality of Minimal PiggyBac Transposons in Mammalian Cells. Mol Ther Nucleic Acids. 2016;5(10):e369.