Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.

Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms.

Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.

Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms.

Design and development of engineered receptors for cell and tissue engineering.

Advances in synthetic biology have provided genetic tools to reprogram cells to obtain desired cellular functions that include tools to enable the customization of cells to sense an extracellular signal and respond with a desired output. These include a variety of engineered receptors capable of transmembrane signaling that transmit information from outside of the cell to inside when specific ligands bind to them. Recent advances in synthetic receptor engineering have enabled the reprogramming of cell and tissue behavior, controlling cell fate decisions, and providing new vehicles for therapeutic delivery.

Enhanced regulation of prokaryotic gene expression by a eukaryotic transcriptional activator.

Expanding the genetic toolbox for prokaryotic synthetic biology is a promising strategy for enhancing the dynamic range of gene expression and enabling new engineered applications for research and biomedicine. Here, we reverse the current trend of moving genetic parts from prokaryotes to eukaryotes and demonstrate that the activating eukaryotic transcription factor QF and its corresponding DNA-binding sequence can be moved to E. coli to introduce transcriptional activation, in addition to tight off states.

Biological Cells as Therapeutic Delivery Vehicles.

One of the significant challenges remaining in the field of drug delivery is insufficient targeting of diseased tissues or cells. While efforts to perform targeted drug delivery by engineered nanoparticles have shown some success, there are underlying targeting, toxicity, and immunogenicity challenges. By contrast, live cells usually have innate targeting mechanisms, and can be used as drug-delivery vehicles to increase the efficiency with which a drug accumulates to act on the intended tissue.