Transcription Factors: The New Frontier in Drug Development
Transcription factors, powerful genes that control many others, have long been considered too risky and undruggable by pharmaceutical companies. However, recent advancements in siRNA, omics, and AI/ML technologies are making these master regulators of our biggest diseases, like aging and cancer, more accessible for drug development.
Boehringer Ingelheim is at the forefront of this effort, collaborating with researchers to investigate transcriptional regulators using the SLAMseq method. Additionally, the German preCDD research network includes the TACTIC consortium, focused on developing new cancer drugs by inhibiting transcription. These initiatives aim to overcome traditional challenges, such as lack of defined binding pockets and broad effects of transcription factors.
The potential of transcription factors was first demonstrated in 2006 when Shinya Yamanaka showed that activating a combination of four could revert differentiated cells to pluripotency, earning him the 2012 Nobel Prize in Physiology or Medicine. Now, with mature siRNA, omics, and AI/ML technologies, scientists can understand and unlock the potential of these genes more effectively. However, identifying them as disease drivers and predicting efficacy and safety remain challenges.
These advancements could open a new drug category, leading to a wave of FDA approvals by reprogramming cells back to a healthy state. By targeting transcription factors, we may finally be able to tackle some of our toughest diseases, including cardiometabolic, immunology, inflammation, oncology, musculoskeletal, neurodegeneration, and aging.
