バイオテクノロジーとバイオマテリアル

抽象的な

Precision liquid biopsy based nucleic acid based molecular diagnostics powered by xenonucleic acids

Michael J Powell

Current clinically available molecular tests for detection of pathogenic nucleic acid variations especially tumor derived oncogenic ‘driver’
and drug-resistant somatic mutations that are performed on circulating cell-free nucleic acids present in biological fluids such as patient’s blood
plasma have limited sensitivity. This is because of the low frequency of these gene variations and the large excess of wild-type nucleic acids
present. In order to achieve high sensitivity for the detection of only a few target molecules (mutant alleles) present in a vast excess of non-target
molecules (wild-type alleles) sophisticated methodologies that require expensive instrumentation, highly skilled operators and in some cases
intensive computational bioinformatics methods such as digital-droplet PCR (ddPCR), BEAMing PCR and next generation deep sequencing
(NGS) are being employed in large clinical research centers. The limited availability, high cost and long analysis times of these methods prompted
us to develop a new technology that can be performed globally by existing pathology personnel with instrumentation that is already present in
every hospital pathology laboratory. At the heart of this innovative technology are novel molecular nucleic acid analogs that we call xenonucleic
acids (XNA) that possess all the natural bases that occur in DNA appended to a new chemical backbone that imbibes these oligomeric nucleic
acid binding molecules with exquisite specificity and high binding affinity for complementary target sequences. Any variation in the sequence that
the XNA binds to creates a differential binding phenomena that can be exploited to develop real-time qPCR and extremely high sensitivity NGS
assays that can detect as little as 2 copies of variant templates in a large excess of wild-type templates in DNA obtained from tissue biopsies or
more preferably plasma. Commercial CE/ IVD Certified Products have been developed and validated that include QClampTM gene specific realtime
qPCR based tests, a new highly sensitive blood-based colorectal cancer detection test called ColoScapeTM and a high sensitivity targeted
amplicon based target NGS platform called OptiSeqTM. This presentation will discuss the new technology and the improved and widely available
opportunities that it affords for improved precision diagnostics and targeted therapies of human diseases particularly cancer.