Switching Genes Back On
Christopher Wallace@chris
−6.7%
since Sep 30
The idea
I believe many genetic diseases come from a healthy gene being silenced, not a broken one, so switching it back on can restore normal function without gene replacement. This basket leans into near-term clinical readouts testing that logic, balanced by companies already selling approved RNA-directed medicines and the suppliers who manufacture them regardless of which program wins.
What it owns
- The handful of listed companies whose upcoming trial results directly test whether switching a silenced gene back on works in people. · Ionis PharmaceuticalsIt is running a late-stage trial in Angelman syndrome that aims to reactivate a silenced gene, providing a near-term proof point for whether the mechanism itself is viable., Stoke TherapeuticsIt restores the healthy SCN1A copy in Dravet, applying the same restore-missing-protein logic to a disease already in patients., Wave Life SciencesIt tests RNA editing in the clinic, correcting gene expression without cutting DNA, which follows the no-gene-replacement path the take maps., PTC TherapeuticsIt already sells splice-modifying drugs that change how much protein a gene makes, proving that adjusting gene output is a real commercial business.30%
- Companies already selling RNA medicines at scale, so the take still earns if any one rare-disease trial misses. · Alnylam PharmaceuticalsIt sells RNA-directed medicines profitably, so the take earns on RNA-based rare disease programs regardless of which single trial succeeds., Arrowhead PharmaceuticalsIts RNA silencing pipeline runs many programs with the same delivery chemistry, so the take earns as long as partnered programs advance., BiogenIt sells Spinraza, the proof that an antisense therapy for a rare neurological disease can be a real commercial drug., NovartisIt keeps buying into RNA medicines, so the take bets that the class attracts major capital regardless of which small sponsor wins.20%
- The manufacturing and tooling base that gets paid for every one of these drugs made, whoever ends up owning the winner. · Agilent TechnologiesIt makes the oligonucleotides these drugs are built from, so it gets paid on manufacturing volume regardless of which company wins a trial., DanaherIt sells the tools and bioprocessing gear the whole genomic medicine field runs on, the widest version of the supplier bet., RepligenIt owns bottleneck steps in making RNA and editing medicines, so approved drugs from any sponsor mean more of its revenue., Charles River LaboratoriesIt runs the preclinical studies every rare-disease and gene-editing program has to pass through, paid as long as that spending stays funded., Twist BioscienceIt supplies the synthetic DNA that editor and RNA programs are designed with, upstream of everyone in the take.17%
- Public proxies for the private epigenetic editing field, companies building tools that rewrite or re-regulate genes without replacing them. · Beam TherapeuticsIt is the leading listed proxy for programmable editing and needs precise, non-cutting edits to keep advancing in human trials., Intellia TherapeuticsIt proves in vivo gene editing at scale is possible, showing whether delivery is solved enough for epigenetic editors to follow., Prime MedicineIts editing approach is precise enough in principle to change one gene without touching hundreds, the core precision problem the take addresses., Editas MedicineIt has moved toward turning genes up rather than knocking them out, the closest listed version of undoing a silenced gene switch.12%
- The X-linked and rare neurological diseases this mechanism targets, plus the hard problem of getting a drug into the brain. · Denali TherapeuticsMost X-linked targets and rare neurological diseases live in the brain, and its blood-brain-barrier delivery platform is how these medicines reach them., Taysha Gene TherapiesIts Rett gene therapy is the competing approach that reads directly on whether Rett is treatable and whether reactivation has to beat replacement., NeurogeneIt adds self-regulating gene therapy in Rett, tackling the dosing problem that reactivation logic sidesteps.8%
- Cash12%