Gene Circuits Empower Next-Generation Cell and Gene Therapies

Over the past few decades, we have seen remarkable advances in technologies for reading (sequencing) and writing (synthesizing) DNA. These technologies have enabled us to decipher disease. Now they are allowing us to program “living medicines” —cell and gene therapies that reprogram genetic code.

Traditional drugs, namely, small molecules and biologics, typically target proteins and block their function. These drugs are static. They have a predefined activity that can’t be adapted once they are delivered into patients. Living medicines, however, are dynamic. That is, they provide sense-and-respond functionality.

As transformative as living medicines promise to be, they are still confined to narrow applications, having been of proven effectiveness against only a few monogenic diseases and hematological malignancies. Current approaches are limited to sensing and correcting single disease signatures, and they provide little control over their dosage, timing, or localization. These shortcomings can be overcome if synthetic biology is used to create the next generation of cell and gene therapies. These therapies will be programmable, and when they are broadly adopted, they will help treat, or even cure, many complex diseases.

Programming cell and gene therapies with synthetic biology

Synthetic biology applies engineering principles to program living systems, enabling them to perform user-defined functions. By leveraging advances in our ability to read and write DNA, we can engineer cells that incorporate artificial multigene constructs, referred to as gene circuits, that allow cells to make decisions and produce a desired response.

Gene circuits are the “software” that can be deployed into virtually any cell or gene therapy modality (the “hardware”) to create adaptive therapies that can address many different disease areas. Programming biological systems with gene circuits can overcome the shortcomings of existing cell and gene therapy approaches by making them more controllable, targeted, and effective via multimodal activity.

This is currently being developed for cancer but may be suitable for a wide variety of diseases that could potentially be treated with cell or gene therapy.

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