Development of the mRNA Therapeutic—Not Warp Speed!

Triple-negative breast cancer accounts for a disproportionate share of the total breast cancer morbidity rate due to its aggressive behavior and lack of effective targets.Join Dr. Brian Adams of Harvard Medical School as he discusses how microRNAs can serve as superior therapeutic agents in the fight against triple negative breast cancer.

MicroRNA(miRNA) are short non-coding single-stranded RNA molecules that regulate gene expression at the post-transcriptional level. They are known to play a critical role in multiple biological processes including proliferation, differentiation, apoptosis, and hematopoiesis. Dysregulation of miRNA expression, therefore, is associated with a number of pathological conditions such as inflammation, cardiovascular diseases, neurological disorders and several types of cancers. miRNAs are also found to be extremely stable in body fluids such as serum, plasma, urine, breast milk, and saliva. Extracellular miRNAs are either packed into exosomes or loaded into high-density lipoproteins or bound by AGO2 proteins outside on vesicles. These modes of action protect miRNAs from degradation and improve their stability. Because of their stability in body fluids, miRNAs are gaining importance as biomarkers in liquid biopsies.

Large-scale sequencing of human tumors has uncovered a vast array of genomic alterations. Genetically engineered mouse models recapitulate many features of human cancer and have been instrumental in assigning biological meaning to specific cancer-associated alterations.

Cardiac excitation-contraction coupling is the process by which electrical excitation drives cardiomyocyte mechanical shortening. Following membrane depolarization, calcium influx through voltage-gated calcium channels triggers calcium release from intracellular stores. Increased cytosolic calcium binds to troponin, allowing sliding of actin thin filaments against myosin thick filaments. This results in myocyte contraction. Cytosolic calcium extrusion and sequestration induces myofilament relaxation, readying the cardiomyocyte to begin again. Understanding this tightly regulated process, as well as how perturbations disrupt it, is critical to understanding heart function and dysfunction.