Targeted Cancer Therapy: How Artificial DNA is Changing the Game

 




Cancer is one of the world's most daunting health challenges, affecting millions of individuals each year. Traditional cancer treatments, such as chemotherapy and radiation, are frequently associated with considerable side effects and poor efficacy, especially against aggressive or resistant tumors.

The fundamental difficulty with conventional cancer treatments is their lack of specificity. Chemotherapy and radiation both target fast dividing cells, which are indicative of cancer. However, these treatments make no distinction between malignant and healthy cells, resulting in massive collateral harm. This causes a variety of unpleasant side effects, including hair loss, exhaustion, immune system suppression, and more. Furthermore, certain tumors acquire resistance to these medicines over time, reducing their effectiveness and leaving patients with fewer treatment options.

Another significant issue in cancer treatment is the capacity to specifically target cancer cells while avoiding harming healthy cells. This has been especially difficult in the creation of nucleic acid-based medications, which use DNA or RNA molecules to disrupt sick cells' biological functions. Although nucleic acid therapies offer tremendous potential, they have struggled to distinguish between malignant and normal cells, resulting in unexpected and perhaps detrimental immune responses.

Artificial DNA to Target and Kill Cancer Cells

A revolutionary strategy to targeting and killing cancer cells has been devised, which employs artificial DNA. This novel technique entails the creation and manufacture of hairpin-shaped DNA molecules that are particularly tailored to attack cancer cells while protecting healthy tissue. Oncolytic hairpin DNA pairs (oHPs) are chemically produced DNA molecules structured like hairpins. These oHPs are programmed to respond to certain microRNAs (miRNAs) that are overexpressed in certain cancer cells. When these DNA pairs reach cancer cells, they interact with miRNAs, triggering a unique series of events that eventually destroys the malignant cells.

The capacity of this artificial DNA-based treatment to precisely target cancer cells contributes to its efficacy. Cancer cells frequently overexpress particular miRNAs, such as miR-21, which are significantly lower in healthy cells. The oHPs are engineered to specifically recognize and bind to these overexpressed miRNAs, ensuring that the treatment is focused on cancer cells while limiting the danger of harming healthy cells.

When oHPs enter a cancer cell, they interact with overexpressed miR-21, causing the hairpin DNA to unwind and create longer DNA strands. This structural shift is noticed by the cell's immune surveillance mechanisms, which see irregular DNA creation as a threat. The immune system then launches a response against the cancer cells, successfully eliminating them while leaving healthy cells alone. This targeted technique has a substantial benefit over standard cancer treatments since it decreases the possibility of adverse effects while increasing treatment efficacy. This strategy presents a fresh way to attack cancer by utilizing the body's natural immune response, which has the potential to overcome the limits of current medicines.

How Artificial DNA Activates the Immune Response

The mechanism underlying this artificial DNA-based treatment is novel and very targeted. In their native, compact hairpin shape, oHPs are inactive and do not elicit an immunological response. When they interact with their target miRNA, such as miR-21, they undergo a conformational shift, unfolding and creating longer DNA strands.

The cell recognizes this newly produced DNA structure as an anomaly, triggering an immunological response. The immune system perceives the presence of these lengthy DNA strands as an indication of infection or another threat, triggering an innate immune response. This response is especially effective in eliminating cells that overexpress the miRNA, which results in the selective death of cancer cells.

The distinctiveness of this mechanism is what makes it so appealing. Unlike conventional treatments, which might destroy healthy cells, this technique targets just cancer cells. This not only improves the treatment's efficacy but also considerably lowers the likelihood of side effects, making it a potentially revolutionary advancement in cancer therapy.

REFERENCE:

Morihiro, K., Osumi, H., Morita, S., Hattori, T., Baba, M., Harada, N., ... & Okamoto, A. (2022). Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly. Journal of the American Chemical Society145(1), 135-142. https://doi.org/10.1021/jacs.2c08974

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