Edwin Neumann (BLAINEY & WEISSMAN LABS)

Engineering a Compact Epigenome Editor to Treat Fatal Prion Disease

Epigenome editing offers lasting gene repression without DNA damage. Editors like CRISPRoff confer durable, targeted transcriptional silencing through DNA methylation at gene promoters but have limited therapeutic potential due to toxicity and large transgene size. We solve this by developing CHARMs: compact, nontoxic effectors that enable epigenome editing in the CNS. We demonstrate robust silencing of the prion protein in mouse brains using AAV-mediated delivery of CHARMs, paving the way for treatment of fatal prion diseases.

Alex Hostetler (IRVINE LAB)

Boosting CAR T Cells for a Universal Solid Tumor Therapy

While CAR T cell therapy has been successful in treating some blood cancers, there has been no success in patients with solid tumors. To overcome the challenges faced in solid tumor settings, we developed a method to vaccine boost CAR T cells using an amphiphilic CAR ligand that results in massive CAR T expansion. The boosted CAR T cells induce spreading of neoantigens which prime endogenous T cells. We further utilized the amph-ligand to decorate solid tumors, effectively creating a tumor-agnostic CAR T cell therapy for solid tissue cancers.