The emergence of messenger RNA (mRNA) technology, highlighted by the success of Covid-19 vaccines, has spurred widespread interest in its applications. Beyond preventive vaccines, scientists are exploring the potential of mRNA in treating diseases, particularly cancer.
However, a significant challenge lies in delivering mRNA to specific locations in the body. Lipid nanoparticles have been used to transport mRNA, but they lack the precision needed for cancer treatment, as many cancer therapies can be toxic to off-target tissues.Â
Addressing this challenge, Boston-based Strand Therapeutics has developed a groundbreaking approach, receiving approval from the US Food and Drug Administration (FDA) for the first-ever clinical trial testing programmable mRNA therapy in cancer patients with solid tumors. The programmable aspect involves coding mRNA like computer instructions, enabling it to perform specific functions, such as activating only in certain cell types, at specific times, and in specific amounts.Â
In the context of cancer treatment, synthetic mRNA directs cancer cells to produce specific proteins that alert the immune system to the presence of tumors. Strand’s therapy focuses on generating an inflammatory protein called interleukin-12 (IL-12). This protein triggers immune cells to initiate a sequence of events leading to the targeted destruction of cancer cells. The mRNA essentially acts as a programming tool, causing the tumor to become a factory for producing the desired protein.Â
IL-12 has long been considered a potential cancer therapy, but early trials in the 1990s faced challenges due to severe side effects when the protein was delivered directly into the bloodstream. Despite attempts to create safer versions, interest from major pharmaceutical companies dwindled. Strand’s innovation revolves around a genetic circuit that instructs the mRNA to produce IL-12 only in the tumor microenvironment, eliminating the risk of off-target effects. The genetic circuit is designed to sense microRNA levels, which differ between cancer and healthy cells.Â
To ensure the therapy’s precision, the mRNA is engineered to self-destruct if it goes anywhere other than the intended tumor. Initially, the clinical trial will focus on easily accessible tumors, such as melanoma and breast cancer, with mRNA injected directly into the tumors to assess the localized effect. Future plans include exploring body-wide infusions for treating tumors in remote locations, with the therapy selectively activating in specific cells and tissues.Â
While injecting the mRNA at the tumor site provides localized effects, the programmable approach offers an added layer of safety. Monitoring IL-12 levels in the blood will allow researchers to ensure that the protein remains confined to the tumor, minimizing the risk of unintended side effects.Â
Strand’s programmable mRNA therapy marks a significant advancement in the field, and its success in the clinical trial could pave the way for more sophisticated applications of genetic circuits in creating highly precise therapies. However, the trial will also assess the reliability of the genetic circuit, as occasional mistakes could impact safety and efficacy. The potential of genetic circuits lies in their ability to match the complexity of biological systems, offering a promising avenue for developing more targeted and sophisticated therapies.Â
As mRNA technology continues to evolve, its applications in treating diseases like cancer hold immense promise, and innovations like Strand’s programmable approach contribute to the growing landscape of precision medicine. The upcoming clinical trial will provide crucial insights into the feasibility and effectiveness of this pioneering mRNA therapy, offering hope for more effective and targeted cancer treatments in the future.Â
News Reference Â
WIRED, https://www.wired.com/story/cancer-hunting-mrna-programming-treatment-test/.
