Out-licensing

Engineering Pseudomonas Exotoxin A for Nucleic Acid Delivery: No Cell Type Specificity or Sequence Specificity Required

Introduction/Background

Nucleic acid delivery into cells, including the cell nucleus, can be accomplished by viral and non-viral means. For example, retroviruses and adeno-associated viruses are efficient delivery vehicles often used in gene therapy protocols, even though safety concerns over the use of viruses in humans remain. These concerns have prodded the development of non-viral delivery means, such as the use of liposomes to encapsulate nucleic acids. Unfortunately, non-viral delivery vehicles are generally inefficient when compared to viral vectors, due in part to cellular compartmentalisation and degradation of the nucleic acid taken up by a cell.

Aims/Hypothesis

The aim is to develop a system for the delivery of any nucleic acid safely.

Research

The invention is a newly engineered PE (Pseudomonas exotoxin A) derivative protein, whose ADP-ribosylation domain has been replaced by the human topoisomerase I DNA binding domain. The Top I DNA binding domain can bind negatively charged DNA strongly without sequence specificity. This PE derivative can then enter cells through the LDL-receptor mediated endocytosis pathway, then the translocation domain of this PE derivative can translocate into the cytosol. The DNA would eventually enter the nucleus.

Conclusion

This technique can use to deliver any nucleic acids without sequence specificity into the cells and organisms.

Relevance/Opportunity

Please enquire regarding the formation of licensing partnerships quoting reference no. 13A-880308.

Preclinical

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