TransCode believes it has solved one of the major challenges facing targeted therapeutic delivery to cancer
A therapeutic (re)purpose
The TTX delivery system is built around a core iron oxide nanoparticle that minimizes early kidney and liver clearance. This translates into a long circulation half-life that allows for efficient accumulation in tumors and metastatic sites. These particles have an excellent clinical safety record of low toxicity and low immunogenicity. Their built-in imaging capabilities have the bonus of enabling quantification of the particles’ delivery to target organs. The core iron oxide complex is cross-linked with dextran, a glucose polymer, to provide overall stability to the particle. The dextran coated iron oxide cores are functionalized with amino groups to provide stable links through disulfide bonds to the therapeutic oligonucleotides of interest and other therapeutic payloads.
The small hydrodynamic size and positive charge of the resulting nanoparticles allow them to infiltrate the tumor microvasculature, extravasate into the interstitium of tumors and metastases, and be readily taken up by the cells. The coating with dextran further facilitates the rapid uptake of the particles by exploiting the high metabolic activity of cancer cells, a process analogous to the mechanism behind the systemic loading of metastatic cancer cells with fluorodeoxyglucose (FDG) for diagnostic PET imaging. The combined result of a hydrodynamically favored distribution and a metabolically triggered uptake result in the enhanced ability of TransCode’s nanoparticles to access genetic targets inside tumor cells.
The TTX delivery system is built around a core iron oxide nanoparticle that minimizes early kidney and liver clearance. This translates into a long circulation half-life that allows for efficient accumulation in tumors and metastatic sites. These particles have an excellent clinical safety record of low toxicity and low immunogenicity. Their built-in imaging capabilities have the bonus of enabling quantification of the particles’ delivery to target organs. The core iron oxide complex is cross-linked with dextran, a glucose polymer, to provide overall stability to the particle. The dextran coated iron oxide cores are functionalized with amino groups to provide stable links through disulfide bonds to the therapeutic oligonucleotides of interest and other therapeutic payloads.
The small hydrodynamic size and positive charge of the resulting nanoparticles allow them to infiltrate the tumor microvasculature, extravasate into the interstitium of tumors and metastases, and be readily taken up by the cells. The coating with dextran further facilitates the rapid uptake of the particles by exploiting the high metabolic activity of cancer cells, a process analogous to the mechanism behind the systemic loading of metastatic cancer cells with fluorodeoxyglucose (FDG) for diagnostic PET imaging. The combined result of a hydrodynamically favored distribution and a metabolically triggered uptake result in the enhanced ability of TransCode’s nanoparticles to access genetic targets inside tumor cells.
Our Expanding Delivery Platform
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Employing the proprietary TTX delivery platform, TransCode Therapeutics has created seven distinct product families of therapeutic candidates with the objective of improving cancer patient outcomes and ensuring long-term survival. Our lead therapeutic candidate, TTX-MC138, currently our primary focus, is targeting metastatic cancer, which has been shown to be responsible for the majority of all cancer deaths annually.
Currently we are continuing research on a variety of both diagnostic and therapeutic approaches targeting biomarkers broadly prevalent across numerous tumor types.
* TransCode signed Exclusive Option Agreements with The General Hospital Corporation, d/b/a Massachusetts General Hospital, or MGH, for TTX-siLin28b and 64Cu-TTX-MC138. Under these Options, TransCode has the right to negotiate a license for these candidates with MGH. TransCode’s decision will depend on the results of preclinical studies it plans to conduct as shown above.
** Seeking Orphan designation status *** Received Orphan designation status from FDA Additionally, TransCode’s other drug candidates, TTX-siPDL1, 64Cu-TTX-MC138, TTX-siLIN28b, TTX-RIGA, TTX-CRISPR and TTX-mRNA, focus on treating cancer using RNA technology made possible through our proprietary delivery platform.
Learn more about how TransCode is advancing new RNA therapies through a modular design engine.
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