Second Generation Antibody Therapy
The top 6 commercially produced antibodies in the marketplace currently generate revenues totaling approximately $25 billion. VIRxSYS has preliminary data that encourages further evaluation of the feasibility of utilizing its SMaRT™ technology to induce patients to manufacture certain required antibodies in their own bodies, replacing the commercial manufacturing of anti-bodies which are currently injected into a patient.
The Company has performed some early work in applying the SMaRT™ technology platform to the generation of antibodies in vivo. This would work as follows: VIRxSYS lentiviral vector would be re-engineered to have an affinity to a specific cell type (e.g. a liver cell). These cell-specific vectors would also be constructed to carry a certain gene payload. The gene payload selected would be one that can reprogram, or hijack, a certain gene in the targeted cell. When VIRxSYS’ lentiviral vector delivers the gene to the cell, the hijacked gene in that cell would then be re-programmed to produce the desired antibody protein. This anti-body protein, would then be secreted into the plasma, migrate throughout the body and attach itself to its specific and disease related protein. Once it binds to its specific disease-related target, this anti-body would interfere with the disease, hopefully providing therapeutic relief. The patient benefit of this approach is that the hijacked gene may be able to produce the desired antibody protein for up to 6 to 9 months, and possibly longer, compared to anti-body injections lasting only up to a dozen days or so.
This is an early stage project and could take several years before entering into human clinical trials. However, proof of principle has been demonstrated in mice, showing that the antibody molecule could be detected in the blood just eight hours following administration. This approach of having the body manufacture antibodies in vivo would have many benefits including a lower manufacturing cost and a longer anti-body impact in a patient. The Company has already presented this antibody strategy to potential strategic partners and interest in this approach has been high.
Stem Cell Applications
Stem cell applications hold great promise. VIRxSYS believes that our platform technologies of gene delivery (lentiviral vectors) and gene re-programming (SMaRT™) can make significant contributions to the research and development of therapies using adult stem cells, specifically induced pluripotent stem (iPS) cells, which avoid the use of embryonic stem cells and the potential ethical issues surrounding their use. Our scientists are working with the Johns Hopkins University on these latest stem cell approaches, and we are very excited about the future potential of this collaboration. VIRxSYS has recently received a competitive grant from the State of Maryland to study the applications of SMaRT™ and lentiviral vector delivery to iPS cells. Studies financed by this grant began in the summer of 2009.
SMaRT™ Image (Molecular Imaging)
SMaRT™ Image can be used to perform real time molecular imaging of gene expression and has potential applications both in pre-clinical research and human diagnostics. SMaRT™ has the ability to trans-splice any reporter gene into essentially any expressed pre-mRNA that contains introns to provide truly real time molecular imaging.. Reporter genes that encode fluorescent or luminescent proteins may be used for optical imaging; other reporters such as thymidine kinase make the technology adaptable to positron emission tomography (PET). In pre-clinical research, imaging can be applied in target validation, drug discovery or drug and vector distribution.
Advantages: SMaRT™ Image offers several advantages over conventional imaging methods.
Direct approaches to molecular imaging traditionally employ molecules such as antibodies that interact with the gene product of interest. Screening for new molecules is labor intensive and reduces the rate at which new imaging reagents can be developed. SMaRT™ allows for the rapid development of new imaging molecules. The PTMs used for molecular imaging will have two standard coding sequences, that of a fluorescent/luminescent or PET reporter, and will differ only in the binding domain which is specific for each target pre-mRNA. This modular nature of the PTM is a distinct advantage of SMaRT™ Image.
There have been two publications on molecular imaging in top-tier medical journals, the Proceedings of the National Academy of Sciences USA 101:8693, 2004) and the Journal of Nuclear Medicine (49:1146, 2008). In a commentary accompanying our article in the Journal of Nuclear Medicine¸ a leading scientist in the field wrote, “This study represents an important step toward a universal imaging methodology of an endogenous mRNA target, with potential applications in research and diagnostics.” V. Ponomarev, Memorial Sloan Kettering Cancer Center. J. Nucl. Med . 49:103501037, 2008.