Programming gene and engineered-cell therapies with synthetic biology

Abstract

Gene and engineered-cell therapies promise to treat diseases by genetically modifying cells to carry out therapeutic tasks. Although the field has had some success in treating monogenic disorders and hematological malignancies, current approaches are limited to overexpression of one or a few transgenes, constraining the diseases that can be treated with this approach and leading to potential concerns over safety and efficacy. Synthetic gene networks can regulate the dosage, timing, and localization of gene expression and therapeutic activity in response to small molecules and disease biomarkers. Such "programmable" gene and engineered-cell therapies will provide new interventions for incurable or difficult-to-treat diseases.

Multiplexed biosensors for precision bacteria tropism in vivo

“…Main Text: Microbiome research continues to demonstrate the abundance of microorganisms in various environments (1-3). An emerging focus in synthetic biology engineers microbes to integrate within specific niches in nature, artificial infrastructure and the human body (4)(5)(6)(7)(8)(9)(10)(11). Since genetic programming of bacteria enables them to sense and respond to physiological conditions in situ, this approach is poised to change existing paradigms for diagnosing and treating diseases such as inflammation (12,13), infection (14,15), and cancer (16)(17)(18).…”

Are Current Strategies for Building a Human Kidney Misguided? Speculative Alternatives

“…This is entirely feasible using modern regenerative and stem cell technologies. 16 As an example, "gut-on-a-chip" experiments have shown that colonic epithelia in vitro form folds that increase the surface area exposed to the lumen. 17 An array of engineered cell types could be created from induced pluripotent stem cells, each designed to deliver specific ions and solutes into the lumen of the colon or the urinary bladder.…”

Engineering multiple levels of specificity in an RNA viral vector

“…Improved delivery capabilities could enable new generations of gene therapy that take advantage of advances in synthetic biology to provide increased specificity and control. In fact, synthetic biologists have now developed a broad range of biological circuit designs that sense and respond to endogenous cellular states [1][2][3] . These include systems based on protein-DNA interaction 4 , regulatory RNAs 5 , and protein-level circuits [6][7][8] , as well as combinations of these modalities 9,10 .…”