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Unveiling the potential of cell-free DNA

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The Takeaway: Cell-free DNA, discovered in 1948, is a fascinating and versatile molecule with broad potential in the fields of medicine. First thought to be nothing special, the importance of cell-free DNA (cfDNA) was realized as researchers began to see differences in the cfDNA of individuals who were healthy and had diseases.

What is cfDNA?

Cell-free DNA (cfDNA) are fragments of DNA that circulate freely in the blood system and are not contained in cells. These fragments typically range from 150 to 200 base pairs in length and can be derived from a variety of sources, including healthy cells, tumor cells, and even microbes. This genetic material, which is shed by dying or damaged cells, enters the bloodstream and becomes a key piece of information about a body’s physiological state.

What are the research applications of cell-free DNA?

This genetic material is released by cells into the blood, and its analysis has various applications. Here are some research uses of cfDNA:

  1. Cancer research:
    • Early detection: cfDNA can carry genetic mutations or alterations associated with cancer. Analyzing cfDNA permits the early detection of cancer or monitoring cancer progression.
    • Tumor mutational burden (TMB): TMB, a measure of the number of mutations in a tumor's DNA, can be assessed using cfDNA to help characterize tumors and guide treatment decisions.
    • Monitoring treatment response: Changes in cfDNA levels or specific genetic markers can be indicative of a patient's response to cancer treatment. This is useful for optimizing therapeutic strategies.
  2. Infectious disease research:
    • Pathogen detection: cfDNA can carry genetic material from infectious agents, enabling the detection of viral or bacterial infections.
    • Antibiotic resistance: cfDNA analysis can show the presence of genetic markers associated with antibiotic resistance in microbial populations.
  3. Cardiovascular research: cfDNA can be used to study genetic factors associated with cardiovascular diseases. Changes in cfDNA levels may be linked to conditions such as myocardial infarction or heart failure.
  4. Research in aging: Studying cfDNA can provide insights into the aging process, as changes in the amount and composition of cfDNA have been associated with age-related conditions.
  5. Monitoring minimal residual disease (MRD): In cancer research, cfDNA can be used to monitor the presence of residual cancer cells after treatment.
  6. Genomic research: cfDNA can be used for various genomic studies, including the identification of genetic variations, epigenetic changes, and other molecular characteristics.

Research in cfDNA continues to evolve, and its applications are expanding as technology and understanding of the biology of circulating DNA advance.

Challenges in the use of cfDNA

Despite its incredible potential, using cfDNA is not without its challenges. For example, the fragments in the bloodstream may be scarce, which makes their analysis complex and difficult. Researchers are working on improving the sensitivity and specificity of cfDNA testing methods to alleviate this. But there are also privacy concerns and ethical considerations in the widespread use of cfDNA data.

Despite this, the future of cell-free DNA research looks promising. As technology continues to advance, there will likely be more applications in both disease diagnosis and monitoring and also in personalized medicine and drug development. The power of cfDNA rests in its ability to provide real-time information about a body’s health.

cfDNA research solutions from IDT

 Cell-free DNA is a groundbreaking discovery that continues to transform the world of medicine, and IDT’s products and solutions support researchers around the world. The xGen™ cfDNA & FFPE DNA Library Preparation Kit powers research by providing highly complex variant detection from degraded and low-input research samples. This tool permits high conversion rates compared to TA-ligation-based methods with novel ligase and highly modified adapters and allows the ability to identify variants at ≤1% variant allele frequency (VAF).

IDT now sells the Archer™ LIQUIDPlex™ Universal Solid Tumor Panel, which allows researchers to detect important alterations for multiple cancers with one ctDNA panel. The panel targets 29 genes, a hands-on time of just 3.5 hours and a total library prep time of 1.5 days. Learn more here.

Interested in learning more about this technology? IDT’s recent white paper details solutions for superior NGS library complexity and target coverage. Download it for free here.

Engaged in cancer molecular profiling? Research in the discovery and identification of new targetable biomarkers is driven by comprehensive tumor profiling using NGS. But as mentioned, converting tissue samples into NGS libraries can be challenging due to the presence of low-quality or low-quantity DNA. IDT’s MRD research application note explores the use of MRD in low-frequency variant identification.

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