This advancement in gene regulation could enhance gene therapy approaches by enabling targeted modifications to genes in specific cells, thereby minimizing side effects and improving treatment efficacy.

The study represents a significant shift in generative biology, moving the focus from protein design to precise control over gene expression, which is crucial for addressing diseases caused by faulty gene regulation.

A groundbreaking study published in the journal Cell on May 8, 2025, reveals that generative AI can design synthetic DNA molecules to control gene expression in healthy mammalian cells.

The AI model is capable of predicting combinations of DNA sequences necessary to achieve specific gene expression patterns, allowing for the creation of synthetic DNA fragments that can activate genes in targeted cell types.

Key discoveries from the research indicate that while many enhancers can activate genes in one cell type, they may repress genes in another, highlighting complex interactions in gene regulation through a phenomenon termed 'negative synergy.'

In a proof-of-concept experiment, the researchers successfully designed DNA sequences that activated a gene coding for a fluorescent protein in mouse blood cells without disrupting other gene functions.

Researchers from the Centre for Genomic Regulation (CRG) developed an innovative AI tool that generates unique DNA regulatory sequences tailored to specific gene activation requirements.

Over five years, the team synthesized more than 64,000 synthetic enhancers, creating the largest library of synthetic enhancers for blood cells to date, which they examined across various stages of blood cell development.

To build the AI model, researchers generated a substantial dataset through thousands of experiments focused on blood cell formation, utilizing healthy cells for a more accurate biological representation.

The findings lay the groundwork for future research, as many transcription factors and gene regulatory mechanisms remain largely unexplored, presenting opportunities for innovative therapeutic strategies.

Dr. Robert Frömel, the study's lead author, emphasized the transformative potential of this technology for gene therapy, allowing precise adjustments to gene activity in targeted tissues.

AI-generated enhancers can create highly selective regulatory elements, enhancing the precision of therapeutic strategies and minimizing unintended effects on healthy cells.