Congrats to the whole team, and thanks to NIBIB for leading support of this work! If you're interested in trying these parts, check our page on @addgene.bsky.social or drop me a line!

Finally we show how these synthetic receptors can be multiplexed to evaluate soluble signals in the environment to create tailored activation programs that can enable "smart" cell therapies

Examples: cytokine-induced CAR expression on T cells to create a logic gate - the cell is activated only if it sees BOTH a specified soluble cue and surface feature (e.g., tumor antigen), and rewiring cytokine sensing into native pathways that modulate cell state in desired ways

We then leverage the modularity of these converted receptors to link biosensor output to genetic programs, creating new and useful cellular behaviors

We examine a series of natural receptors, each with a unique (and partially understood) mechanism, and by converting them into synthetic receptors (which we call NatE MESA), we learn the rules governing successful conversions

Here we rigorously quantify these challenges (for the first time), develop an assay to overcome this problem, and use this approach to shed new light on delivery phenomena that have previously been elusive and confusing.

More to come with final publication!

However, studying EV-AAV delivery carries unique technical challenges due to co-delivery of AAV and the protein it encodes, termed “pseudotransduction”. This effect can lead to “false” delivery that obfuscates both scientific investigation and technology development.

This can be useful, as enveloping shields the AAV core from antibodies and potentially enables us to use targeting technologies developed for enveloped particles to direct AAV delivery to tissues of interest.

This preprint describes a new method enabling us to study and improve AAV encapsulated by extracellular vesicles (EVs). When cells produce AAV particles, which normally lack an envelope, a certain fraction get naturally incorporated into EVs.

Deadline to apply was just extended to June 5th!

The original deadline for comments of May 23 has been extended to June 7 in response to requests from the public for more time to weigh in, an OMB spokesperson told STAT.

4/n

👀

Congrats to lead author DevinStranford and our collaborators Julius Lucks & Judd Hultquist and teams @NUSynBio!

We believe this technology can be extended to solve all manner of delivery challenges for gene and cell therapy. Check out the story behind the paper and our recent spin-out which is bringing GEMINI to the world through Syenex
 
news.northwestern.edu/stories/2023...

We demonstrate the utility of GEMINI by delivering Cas9-sgRNA CRISPR complexes to primary human T cells to knock out the gene for CXCR4, one of the receptors that HIV uses to infect cells