Biotechnology for Aquaculture

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.

This is a fascinating, exciting, and perplexing time for biotechnology. The industry delivered RNA vaccines to save countless lives during the pandemic and has created impressive early clinical results using CRISPR gene editing to treat patients with deadly genetic diseases.

Antibody-drug conjugates (ADCs) were initially developed to provide a selective targeting mechanism for cytotoxic small molecule drugs with the goal of improving the therapeutic index in clinical practice. But despite a careful target selection and a high degree of specificity afforded through the antibody part of the ADC, a sufficiently improved therapeutic index has been challenging to achieve. It often remains a challenge to reach desirable efficacious doses with repeated cycles of treatment due to the toxicity profile induced by the cytotoxic warhead. The clinical landscape of ADC therapeutics in both hematological and solid cancers has grown in recent years considerably to nearly 600 clinical trials incorporating numerous ADC modalities. These new molecular entities utilize many different tumor-associated antigen targets, new conjugation technologies, and payload warheads of various mechanisms such as tubulin inhibitors, DNA damaging, topoisomerase inhibition, or DNA polymerase II inhibitors.

Understanding the biology of your therapeutic is key to effectively and efficiently progressing it from first principles, through safety assessment studies, and into clinical trials. The unique characteristics and specific biology of each large molecule therapeutic make it impossible to design a “one size fits all” approach to non-clinical development, requiring instead a design tailored to each molecule. For efficient development strategies, this should include a thorough understanding of the disease and therapeutic biology as well as ensuring that the most appropriate studies are conducted to progress each molecule. Despite the need for unique approaches for each novel biologic, there are seven key steps that should be considered when developing biologics through non-clinical development in order to ensure effective and efficient progress.