RootPath Announces Publication Demonstrating How Its Novel Gene Synthesis Technology Empowers Cell Therapy in Solid Tumor Cancers

RootPath, a synthetic biology company that elevates the throughput of gene function interrogation by orders of magnitude, today announced a new publication in Nature Biotechnology detailing research that demonstrates the power of the company’s novel gene synthesis technology and how it may contribute to successful cell therapy in solid tumor cancers. The publication is titled “Discovery of tumor-reactive T cell receptors by massively parallel library synthesis and screening”.

Uncontrollable growth of tumor cells is in part due to the inability of tumor-infiltrating T cells, also known as tumor-infiltrating lymphocytes or TILs, to kill the tumor cells as rapidly as the tumor cells replicate. Methods to boost the number or function of TILs in a tumor, either using drugs or by culturing the TILs outside the patient's body followed by reinfusion, have become a major focus in immuno-oncology research. A key roadblock in these efforts is that TILs are made of a diverse population of cells, among which truly tumor-killing T cells are often of a minority. This is exacerbated by the fact that tumor-killing T cells within TILs are often exhausted and dysfunctional, and do not respond to experimental manipulation so they cannot be effectively identified or enriched.

To solve this, researchers at RootPath and Netherlands Cancer Institute (NKI) led the development of a new technology to create synthetic versions of polyclonal TILs, through massively parallel sequencing and synthesis of T cell receptor (TCR) genes in the TILs. The publication reveals that these synthetic TILs combine the tumor-recognition ability imparted by the TCR genes and the unhampered function of fresh T cells. Using these synthetic TILs, the researchers can readily discover tumor-recognizing TCR genes and can potentially use these genes to create cell therapies for patients with solid tumors. The technology was made possible by a novel sequence design algorithm which enabled the researchers to assemble full-length TCR genes from much cheaper oligonucleotide pools, making the material cost of synthesizing a TCR as low as $1 per TCR gene. The publication further showed that these TCR genes can be introduced to fresh T cells and function correctly, which, combined with novel screening technologies, enables rapid and effective identification of the tumor-recognizing TCR genes.

“This study showcases how advancements in synthetic biology enhance developments in cancer research and cancer therapy,” said Dr. Xi Chen, CEO and co-founder of RootPath and a co-corresponding author of the study. “RootPath is in constant pursuit of cheaper and faster gene synthesis and screening technologies for this reason, and we will make them available as research tools and services to our customers. This publication is an important validator of our mission to drive down the cost of synthesized genes while driving up the throughput of their functional interrogation by orders of magnitude.”

“The sequencing-and-synthesis approach we took in this work offers a great deal of clarity when studying complex systems such as T cell populations. We have previously made this point in a 2019 publication on Nature Medicine, but back then we were only able to synthesize dozens of TCRs. With the help of RootPath’s innovative synthesis technology, we now improved the throughput of this approach by a factor of 100. I believe this technology will be a great catalyst for developing new scientific insights into T cells and ultimately new therapies,” said Dr. Wouter Scheper of NKI, who is a co-corresponding author of the study.

RootPath announced in 2023 that they are offering generic gene synthesis service at a cost of $0.04/bp, which is less than half of the prevailing price on the market. The company will soon offer TCR gene synthesis and screening services commercially, as reported in the study.

About RootPath

RootPath is a synthetic biology company that aims to elevate the throughput of gene function interrogation by orders of magnitude. Our Molecular Programming-based DNA fragment assembly technology gives researchers and drug developers unprecedented, equitable access to long synthetic genes and their functional readouts. As its first vertical application, we apply our technology to mine a patient’s immunome, and help create truly personalized T cell therapies for solid tumors. Together, with leading partners, we are exploring new applications across multiple industries. We enable biology at scale. For more information visit www.rootpath.com

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