New pre-print from the lab!
Customizing AAVs is usually a slow, trial-and-error process. Leveraging mosaic AAVs, Nolan’s new paper presents MATCH, a "plug-and-play" toolkit that clicks homing proteins directly onto the virus.
>80x better brain transduction
>50% transduction of resting PMBCs
Simple one-pot production
full paper: Receptor-guided AAV Tropism Engineering via MATCH https://t.co/A5KEdVUPr7
@Richard_She Indeed, Richard — the choice of linker length and display stalk play a critical role in ensuring signaling responses. There are many applications to explore, and as you noted too, we’re especially excited about the possibilities for combinatorial screening.
Pooled screening of secreted factors (cytokines, growth factors) is difficult due to paracrine cross-talk.
By genetically tethering ligands to the cell surface to enforce obligate autocrine signaling, OASIS enabled a pooled screen of the entire human ligandome (~770 factors) in iPSCs + single-cell Perturb-Seq.
https://t.co/SNngfPXuXy
Regulatable gene expression via endogenous ADAR modulatable Aptamers (Adaptamers).
The system is a compact (<120 bp) cis-regulatory RNA switch. Ligand binding stabilizes a dsRNA motif, recruiting ADAR to edit a premature Stop codon ➔ Sense codon, restoring translation.
• Mechanism: Post-transcriptional, cleavage-free, Stop-to-Sense editing.
• Payload: No exogenous protein regulators required (minimizing immunogenicity/size).
• Validation: Functional in human T-cells; AAV-delivered FGF21 control reversed obesity in mice.
https://t.co/E7rZAp2Y4C
New preprint from the lab led by the amazing Alex Lee, Yesh Doctor, and Yifan Zhang! # high-throughput screening of secreted proteins
"Multiplexed Pan Soluble Ligandome Assaying via OASIS" https://t.co/olPxOIBPtY
New preprint from the lab led by the amazing Jack Bryant!
# tunable genetic medicines, # endogenous ADARs
"Regulatable In Vivo Gene Expression via Adaptamers" https://t.co/214uU0ckxG
3rd generation guide RNA designs for programmable RNA editing via endogenous ADARs https://t.co/YQ2u2dZjtf : work led by the amazing Susan Byrne and Adrian Briggs!