The Dark Matter Project
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darkmatterproject.bsky.social
The Dark Matter Project
@darkmatterproject.bsky.social
Studying The Dark Matter of the Genome - everything noncoding 🧬
A collaborative scientific project at NYU Langone.
Account managed by Ran Brosh.
The final step of engineering is what we call "conversion". It includes introducing Cre enzyme that induces recombination between the 1st loxP site in mouse Taf1 intron 24, and a 2nd loxP site located in human TAF1 intron 24.
October 29, 2025 at 3:30 AM
Next, we engineered mouse embryonic stem cells (mESCs), first with a loxP site in Taf1's intron 24, followed by integration of a marker cassette (a landing pad) downstream of the gene, and finally we replaced this cassette with the 78-kb human fragment.
October 29, 2025 at 3:30 AM
We assembled this region from an XDP patient-derived BAC, using the superpower of S. cerevisiae (yeast), into a delivery-ready vector.
October 29, 2025 at 3:30 AM
Our solution? A "hybrid-convertible" allele:
October 29, 2025 at 3:30 AM
How could one engineer a mouse carrying a LETHAL allele? A thread 🧵
October 29, 2025 at 3:30 AM
One step closer to an LLM that understands novel DNA🧬

𝗜𝘁𝗲𝗿𝗮𝘁𝗶𝘃𝗲 𝗶𝗺𝗽𝗿𝗼𝘃𝗲𝗺𝗲𝗻𝘁 𝗼𝗳 𝗱𝗲𝗲𝗽 𝗹𝗲𝗮𝗿𝗻𝗶𝗻𝗴 𝗺𝗼𝗱𝗲𝗹𝘀 𝘂𝘀𝗶𝗻𝗴 𝘀𝘆𝗻𝘁𝗵𝗲𝘁𝗶𝗰 𝗿𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗴𝗲𝗻𝗼𝗺𝗶𝗰𝘀.

pubmed.ncbi.nlm.nih.gov/41125441

Congrats Andre Ribeiro-Dos-Santos and Matt Maurano!
October 25, 2025 at 1:10 PM