Jennifer R Hamilton

I’m excited to share our work developing an antibody-directed strategy for delivering genome engineering tools to specific cell types, both outside and inside the body 🎯

Hello! Anyone on here a member of ASH? I’m looking for someone who could sponsor a late-breaking abstract. If you can help or make an intro, please DM me. Thanks! 🙏

From exploring bio-entrepreneurship to securing $1 million in non-dilutive funding, the HS Chau WIES award transformed my career. This program empowers women interested in enterprising science; if that's you, apply now! Applications for the next cohort are due April 12 👩‍🔬

This research was a true team effort! It was such a privilege to work on this project in the @doudna_lab with @evelyn_chen11, @b_s_perez, @CindySE27, Min Hyung Kang, Marena Trinidad, and @WayneNgo1. And a big thank you to @igisci for championing this work!

We are excited about this approach’s potential to leverage programmable targeting molecules for delivering genome editors (or other cargo!) to specific, therapeutically relevant cell types inside the body. We are grateful to our collaborators & funders for enabling this project🙏

Specific delivery is challenging to achieve in vivo, with vector uptake often seen in the liver. Excitingly, IV tx w/ antibody-targeted Cas9-EDVs and lenti did not result in broad liver delivery. We observed CAR/mCherry expression in CD3+ T cells but not beta-catenin+ hepatocytes

Antibody-targeted delivery is maintained in vivo. Using PBMC-humanized mice, we were able to deliver both a lentiviral-encoded CAR transgene and Cas9 RNPs to human T cells via a systemic injection, enabling the generation of CAR T cells, with or without gene editing, in vivo

Multiplexing antibody-based targeting molecules on the outside of Cas9 enveloped delivery vehicles (Cas9-EDVs) improves delivery to specific cellular sub-populations. Targeting molecules binding both CD3 and CD4 boosts genome editing in human T cells expressing both ligands:

Here, we are no longer restricted to the native repertoire of naturally occurring viral glycoproteins for cell-selective delivery. Cas9 genome editor delivery can be directed via antibody-fragments to cognate ligand-expressing cells while leaving the bystander cells unmodified:

We previously demonstrated that enveloped lentivirus-like particles packaging Cas9 RNPs could direct genome editing activity to specific cell types based on the inherent, cell-targeting tropism of viral glycoproteins: cell.com/cell-reports/pdfExt…