RootPath Announces Publication Demonstrating How Its Novel Gene Synthesis Technology Empowers Cell Therapy in Solid Tumor Cancers
23 Abril 2024 - 8:30AM
Business Wire
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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