DNA launched (single round) viral vectors

Overview

Ascend is a cancer immunotherapy company developing therapies for primary, recurrent and metastatic cancers. Cancers are comprised of multiple cell types that can influence and promote tumour growth.  There is an emerging view that targeting key cells within the host microenvironment can lead to more robust clinical outcomes.  Ascend is advancing a non-viral approach to efficiently introduce therapeutic genes into the tumour microenvironment (TME), based on its SRIP technology.  The SRIP plasmid vector launches a single round of infectious particles (SRIP). These SRIP vectors then deliver (transduces) replicon RNAs into cells within the local microenvironment. The replicon RNA is self-amplifying and can lead to high levels of persistent gene expression. 

Current Limitations

To date, the translation of targeted non-viral cancer gene therapy has been hampered by limited in vivo transfection efficiency at targeted tissue sites, and a general inability to achieve clinically meaningful levels of therapeutic gene expression. We believe that the use of the SRIP platform can provide two important advancements over the current state of the art.  The first is the ability to preferentially deliver the gene therapy vector to targeted disease sites, and secondly to enable efficient transgene expression.

Targeting the Tumor Microenvironment

Over the last decade there has been increasing recognition that durable clinical responses in cancer patients can be achieved by targeting key immunological processes within the tumor microenvironment.

srip

SRIP represents a novel approach to delivering meaningful levels of transgene expression within the TME.  The SRIP DNA plasmid can be administered intralesionally or conjugated to targeting agents for selective delivery to disease sites.

References

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  4. Reynard, O., Mokhonov, V.,Khromykh, A. A. & Volchkov, V. E. (2011). Kunjin virus replicon-based vaccines expressing Ebola virus glycoprotein GP protect the guinea pig against lethal Ebola virus infection. The Journal of Infectious Diseases 204 Suppl 3, S1060-1065
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  6. Roby, J. A., Hall, R. A. & Khromykh, A. A. (2013). West Nile virus genome with glycosylated envelope protein and deletion of alpha helices 1, 2, and 4 in the capsid protein is noninfectious and efficiently secretes subviral particles. Journal of Virology 87, 13063-13069.
  7. Setoh, Y. X., Prow, N. A. Khromykh, A. A. & Hall, R. A. (2012). Identification of residues in West Nile virus pre-membrane protein that influence viral particle secretion and virulence. The Journal of General Virology 93, 1965-1975.