Frost & Sullivan's 2006 Technology Innovation Of The Year Award in vector technologies for gene therapy and genetic vaccination is conferred upon Mologen AG of Germany, in recognition of the company's development of the Minimalistic Immunogenically Defined Gene Expression (MIDGE) vector technology.
This technology represents an innovative molecular tool that helps in the safe and effective transfer of genetic information into somatic cells, and will thus facilitate the battle against difficult-to-treat human diseases.
In principle, the gene therapy of several life-threatening diseases including cancer involves treating or preventing them by the transfer of the correct or correcting genetic information into the affected body cells. One of the key problems in gene therapy and genetic vaccination is finding a suitable gene carrier (a vector) to transfer the gene into target cells, and subsequently provides sufficient levels of expression. Moreover, a vector to be useful in human gene therapy needs to address many more parameters such as tissue specificity, small size but huge DNA carrying capacity, non vectorimmunogenicity, simple manufacture procedures, combined to a high stability under a broad range of storage conditions, said a press release from the company.
Traditionally, such vectors are either modified viruses, often derived from pathogenic viruses, or recombined bacterial plasmids. All of these have several disadvantages, such as anti-vector immunogenicity, limited transport capacities, poor or no tissue specificity or a considerable content have unwanted respectively unneeded DNA sequences.
Some vectors do not work in nondividing cells. Others require a complex and cost-driving manufacturing procedure. Moreover, viral vectors usually also express viral proteins, which in some cases have led to dangerous and even deadly immunological effects. If, to be functional, the transported genes need to integrate into the host (target) cell genome, viral vectors have recently been reported to cause leukemia and may promote the development of other kinds of cancer. Hence, the lack of an efficient vector with the desired qualities is a major challenge for the research-and medical applications of genetic information.
The MIDGE technology could help overcome such efficacy and safety challenges.
Designed by Mologen researchers, MIDGE vectors are non-viral expression constructs that are characterized by their unique features, particularly by their high safety. MIDGE vectors are made in a two-step process in which the expression cassette is cut out of a suitable plasmid. The resulting fragment of double-stranded DNA, containing the required sequences only, is then sealed by hairpin DNA oligonucleotides at both ends, which results in a linear, covalently closed molecule much smaller than the size of
plasmids.
As MIDGE vectors contain only the expression cassette (promoter, coding sequence, and terminator/poly-A-site), they are able to address the above-mentioned limitations of conventional vectors. Not surprisingly, MIDGE vectors are now being designed for use in both prophylactic and therapeutic vaccination. Clearly, MIDGE vectors have the potential to substitute bacterial plasmid DNA and viral vectors in the field of gene therapy and DNA vaccination, setting new standards in safety and efficacy.