Synthetic Biology's Potential to Address Undruggable Targets and Difficult-to-Treat Diseases

Dear Colleagues,

Traditional small-molecule drugs, while essential to modern medicine, face significant limitations. Their small size and chemical properties can lead to off-target effects and poor bioavailability, and their single-site mechanism of action often results in the rapid onset of drug resistance in diseases like cancer and infectious diseases. Moreover, many potential therapeutic targets, particularly those involved in protein–protein interactions, are considered “undruggable” as they lack the deep binding pockets necessary for small-molecule engagement.

The field of Synthetic Biology, which applies engineering principles to design and construct new biological systems, offers a powerful new constellation of tools for overcoming these challenges. By manipulating DNA to manipulate organisms or systems with novel abilities, synthetic biology enables the development of a new generation of biologics that can address complex biological pathways and targets previously untouched by traditional drug development.

For example, in 2016, eight out of the top ten global best-selling drugs were biologics. In the field of oncology, biologics continue to fill unmet clinical needs that small molecules cannot address. Many monoclonal antibodies such as trastuzumab (Herceptin) have become essential targeted therapies in many anticancer drug cocktails. Although antibodies constitute a large class of biologics, as defined by the FDA, biologics also include other proteins, gene-based therapies, cellular products, vaccines, blood, etc. For decades, insulin has been an essential life-saving medicine for diabetic patients. In 2017, the U.S. Food & Drug Administration (FDA) approved a total of 12 new candidates. Additionally, we also observed the first CAR T cell (Kymriah) and gene (Luxturna) therapies approved in 2017.

We welcome original research articles, reviews, and short communications on topics including, but not limited to:

• Novel biologics and advanced therapies for infectious diseases, cancer, and aging.
• Engineering cells, such as CAR-T cells, for enhanced therapeutic efficacy.
• Developing synthetic biology platforms for vaccine development.
• Designing innovative biological systems to modulate or disrupt protein–protein interactions.
• Applying synthetic biology to address undruggable targets.

We are confident that this Special Issue will serve as a valuable resource for researchers and clinicians, showcasing the cutting-edge work at the intersection of Synthetic Biology and medicine.

Dr. Dario Mizrachi
Guest Editor

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• synthetic biology
• protein engineering
• drug development
• biologics
• undruggable targets