TransCode has decoded the major challenge of RNA delivery
A therapeutic (re)purpose
The therapeutic potential of RNA in oncology remains an unrealized promise due to the difficulty in safely and effectively delivering RNA oligonucleotides to tumors. TransCode is now closer to solving this challenge by means of an ingenious exercise in repurposing. The company has developed an RNA delivery platform, the TTX platform, which leverages an iron oxide nanoparticle already approved as a clinical cancer imaging agent and a treatment for iron deficiency anemia as the physical carrier.
The TTX delivery system is built around a core iron oxide nanoparticle that minimizes kidney and liver clearance, which translates into a long circulation half-life that allows for efficient accumulation in tumor cells and metastatic sites. These particles have an excellent clinical safety record of low toxicity and low immunogenicity, and their built-in imaging capabilities have the bonus of enabling quantification of the particles’ delivery to target organs. The iron oxide cores are functionalized with amino groups to provide stable links through disulfide bonds to the therapeutic oligonucleotides of interest. The core iron oxide–oligonucleotide complex is further coated with dextran, a glucose polymer, to protect the oligonucleotides from degradation and to provide overall stability to the particle.
The small hydrodynamic size and positive charge of the resulting nanoparticles allows 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 avidity of cancer cells for glucose, 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 therapeutic potential of RNA in oncology remains an unrealized promise due to the difficulty in safely and effectively delivering RNA oligonucleotides to tumors. TransCode is now closer to solving this challenge by means of an ingenious exercise in repurposing. The company has developed an RNA delivery platform, the TTX platform, which leverages an iron oxide nanoparticle already approved as a clinical cancer imaging agent and a treatment for iron deficiency anemia as the physical carrier.
The TTX delivery system is built around a core iron oxide nanoparticle that minimizes kidney and liver clearance, which translates into a long circulation half-life that allows for efficient accumulation in tumor cells and metastatic sites. These particles have an excellent clinical safety record of low toxicity and low immunogenicity, and their built-in imaging capabilities have the bonus of enabling quantification of the particles’ delivery to target organs. The iron oxide cores are functionalized with amino groups to provide stable links through disulfide bonds to the therapeutic oligonucleotides of interest. The core iron oxide–oligonucleotide complex is further coated with dextran, a glucose polymer, to protect the oligonucleotides from degradation and to provide overall stability to the particle.
The small hydrodynamic size and positive charge of the resulting nanoparticles allows 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 avidity of cancer cells for glucose, 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.
Optimized TTX Platform advantages:
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Advancing new RNA therapies through a modular approach
The TransCode TTX platform for RNA cancer therapeutic development is modular by design, both at the level of the core nanoparticle and of the therapeutic loading. The size, charge, and surface chemistry of the core nanoparticle can be tuned to optimize the particles for the intended target and therapeutic load. The therapeutic load can also be adapted to the specific application being developed, ranging from siRNAs, antisense oligonucleotides, and non-coding RNA mimics to mRNA–based cancer vaccines and CRISPR–based gene repair and replacement platforms. The platform can further be used for developing RNA-targeted radiolabeled therapeutics and diagnostics and other custom products targeting known and novel biomarkers and other genetic elements as they are discovered and validated. Review pre-clinical and clinical evidence supporting TTX delivery
The TransCode TTX platform for RNA cancer therapeutic development is modular by design, both at the level of the core nanoparticle and of the therapeutic loading. The size, charge, and surface chemistry of the core nanoparticle can be tuned to optimize the particles for the intended target and therapeutic load. The therapeutic load can also be adapted to the specific application being developed, ranging from siRNAs, antisense oligonucleotides, and non-coding RNA mimics to mRNA–based cancer vaccines and CRISPR–based gene repair and replacement platforms. The platform can further be used for developing RNA-targeted radiolabeled therapeutics and diagnostics and other custom products targeting known and novel biomarkers and other genetic elements as they are discovered and validated. Review pre-clinical and clinical evidence supporting TTX delivery
