What is ctDNA?

Cell-free DNA (ctDNA) is genetic material expelled by dying tumor cells into the bloodstream. Once in circulation, ctDNA can be collected and analyzed to find the fraction of mutated alleles to normal alleles derived from a patient’s healthy DNA. The wealth of information contained in this analysis creates numerous opportunities for patients to receive minimally-invasive cancer diagnosis and treatment monitoring.

Why liquid biopsy?

As we enter the age of personalized medicine, DNA sequencing is playing an increasingly important role in determining a patient’s optimal treatment plan. Unfortunately, acquiring tumor to sequence often requires performing a tissue biopsy which can be painful, dangerous, and sometimes even impossible, as is the case with both metastatic and early stage cancer. Liquid biopsy, however, offers a viable non-invasive alternative to tissue biopsy. Not only is liquid biopsy minimally stressful for patients, but is also more comprehensive and easily performed at regular intervals. The potential applications of liquid biopsy are vast -- from targeted cancer therapy selection to real-time minimal residual disease (MRD) monitoring to high-risk population screening -- and we believe it will play a critical role in the future of cancer treatment.

What are the technical challenges?

There are two major technical challenges which have impeded the development of a ctDNA assay.

First, concentrations of ctDNA in blood are extremely low -- no more than a few nanograms per milliliter of plasma. At such small quantities of DNA, detecting mutations at low allele frequencies is exceptionally difficult.

Second, there is relatively high background noise due to sequencing errors. Because the rate of random sequencing error (0.1% - 1%) is very close to the allele frequency of a significant number of ctDNA mutations, mutation signals are easily masked and can result in a false negative.

What does AccuraGen have to offer?

We have developed Firefly,  a powerful new technology for suppressing DNA sequencing errors.  Signals as low as 0.02% can be easily detected using Firefly.

In a SNV detection experiment performed on a mixture of gDNA from two different cell lines, a 2% SNV signal is expected  at position 0. Without Firefly, the signal at Position 0 is masked by background noise but with Firefly,a clear SNV signal appears, even at 0.02%.