Innovation that Benefits Patients and Scientists

Nonacus

The mission of Nonacus is to deliver technologies that allow professionals involved in genomic healthcare to use cell free circulating DNA as a of non-invasive diagnostic tool. The company is led by a team of biotechnologists who have an in-depth understanding of genomics and over 35 years of combined experience in genomics healthcare. Nonacus builds upon global experience of genomic healthcare acquired from the UK’s NHS and an international genome project.

If you are a genomics healthcare professional or researcher, the team behind Nonacus fully understand your needs and challenges

Nonacus converts research experience into tools for routine diagnostics that directly benefit patients and scientists. They have developed and offer several cutting-edge products that are not only exceptionally convenient for researchers to use but multiple tests have validated and established their accuracy.

Cell-Free DNA Technology

The core focus of research and development at Nonacus is cell-free DNA (cfDNA) technology.

cfDNA refers to all non-encapsulated DNA that is present in the bloodstream, resulting from apoptosis or necrosis of cells.1 The advent of cfDNA testing has ushered in a revolution in genetic diagnosis because it is both accurate and non-invasive. Sampling is easy as all it requires is a venipuncture.

Although cfDNA is an excellent biomarker, isolating it from blood plasma can be challenging. Nonacus is committed to providing solutions that make isolating and testing cfDNA easy for researchers. The range of products that Nonacus has to offer can be split into three categories:

  • Pre-analytical products
  • Pre-natal diagnostic products
  • Oncology tests

PRE-ANALYTICAL PRODUCTS

Nonacus

The detection of cfDNA from blood can be arduous undertaking because it is present in extremely low quantities, as most cfDNA is regularly cleared by macrophages. The difficulty is only compounded when researchers need to isolate specific types of DNA, such as circulating tumor DNA (ctDNA) or cell-free fetal DNA (cffDNA). These particular types of cell-free DNA types can get contaminated by DNA from degraded white blood cells.2 Pre-analytical products from Nonacus help minimise this contamination and maximise the yield of cfDNA.

  • Cell3 Preserver: This is an evacuated collection tube, made of polyethylene, and is compatible with other disposable collecting equipment. It contains a chemical that stabilises whole blood and prevents the degradation of white blood cells for up to 21 days. The superior material and stabilising properties allow the sample to be shipped globally. This is facilitated by a barcode, which allows for tracking of the sample.
  • Cell3 Xtract: This is an extraction kit and a convenient solution to extract DNA from plasma. It has a fast processing time of 90 minutes, which applies irrespective of the volume of the biological sample. Sample input is flexible, and can range from 1 to 10 ml. This kit delivers low volume of eluted plasma with high concentration of DNA, eliminating the need for a separate DNA concentration step. The kit does not use carrier RNA for extraction, thereby improving the quantification of cfDNA.

PRE-NATAL DIAGNOSTIC PRODUCTS

Nonacus

Traditionally, prenatal diagnostic tests have involved invasive sampling methods such as amniocentesis and chorionic villus sampling. However, cfDNA testing now allows fetal genotyping using maternal plasma, thereby enabling diagnosis through just a maternal venipuncture. Cell-free fetal DNA originates from placental trophoblasts, and is fragmented in maternal blood when placental particles are shed into maternal circulation.3 The main advantage of cffDNA testing is that, unlike invasive methods, it carries a negligible risk of complications such as spontaneous abortion.4 It can also detect fetal anomalies earlier than with traditional techniques. The following testing kits by Nonacus are a means to detect fetal genotype non-invasively:

  • Cell3 Direct RhD: Rhesus D (RhD) positive fetuses carried by RhD negative mothers are at risk of developing anemia and complications such as hemolytic disease of the newborn. The Cell3 Direct RhD is the first kit of its kind that directly tests maternal plasma for fetal RhD genotype. This kit targets exons 5, 7, and 10 of the RhD gene, and can identify whether the baby is RhD positive or negative.
  • Cell3 Direct Fetal Sex Determination: Sex determination becomes particularly important when there is family history of sex-linked disorders, such as X-linked recessive disorders. The only non-invasive technique that has been available so far is obstetric ultrasonography, which lacks reliability. The Cell3 Direct Fetal Sex Determination kit is the first commercially available kit that can determine the sex of the fetus from maternal plasma cffDNA. This non-invasive kit can be used in early pregnancy and delivers results within 3 hours of receiving the sample.

ONCOLOGY TESTS

Nonacus

Genetic profiling in oncology has been revolutionised with the discovery of ctDNA. In patients with cancer, the amount of cfDNA in blood is much higher than in controls because of the increased turnover of cells. The amount is further increased in metastasis, and reduces during attenuation. Genetic profiling of mutations present in ctDNA can help assess tumor origin. Since the ctDNA reflects tumor genome, it can also aid in the diagnosis and monitoring of progression of malignant disease.5

Testing for tumor mutations from ctDNA is an extremely intricate process, not least because of the small quantities of cfDNA available. To put things further into perspective, the ctDNA forms only a small fraction of cfDNA and a given mutation might exist only in a small portion of the available ctDNA. Nevertheless, Nonacus has been able to develop products that are sensitive enough to detect and measure such mutations accurately.

  • Cell3 Target: This kit can work with as little as 10 ng of ctDNA. It has built-in molecular identifiers, which enable the detection of even ultra-low frequency mutations. The panel of genes to be tested can be chosen from a catalogue or customised according to the laboratory’s specifications. The target capture is efficient regardless of panel size, which can vary from 1 gene to 1000 genes. The kit can also be used with cffDNA to detect mutations associated with single gene disorders such as Huntington disease and achondroplasia. Prenatal diagnosis of aneuploidies, such as trisomy 21 (Down syndrome), is also possible.

FUTURE DIRECTIONS

The team at Nonacus believe that only continual research and development can lead to the best products and superior results. So, in addition to the ongoing testing, validation, and improvement of existing products, Nonacus is always working on bringing new and innovative products related to healthcare to the fore. For example, Nonacus is developing a complete workflow algorithm for liquid biopsies that can aid in tracking tumor progress over time as well as testing the efficacy of anti-cancer regimens.

REFERENCES

  1. Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clinica Chimica Acta 2001; 313 (1–2): 139–42
  2. Anker P, Stroun M, Maurice PA. Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system. Cancer Research 1975; 35 (9): 2375–82
  3. Alberry M, Maddocks D, Jones M, Abdel Hadi M, Abdel-Fattah S, Avent N, Soothill PW. Free fetal DNA in maternal plasma in anembryonic pregnancies: confirmation that the origin is the trophoblast. Prenatal Diagnosis 2007; 27 (5): 415–8
  4. Mujezinovic F, Alfirevic Z. Procedure-related complications of amniocentesis and chorionic villous sampling: a systematic review. Obstetrics and Gynecology 2007; 110 (3): 687–94
  5. Akca H, Demiray A, Yaren A, Bir F, Koseler A, Iwakawa R, Bagci G, Yokota J 2013. Utility of serum DNA and pyrosequencing for the detection of EGFR mutations in non-small cell lung cancer. Cancer Genetics 2013; 206 (3): 73–80.