Here are some more #ASGCT2022 poster and presentation highlights:

• Poster #589: Yecuris shows that GalNAc siRNA can knock down human C5 produced by human hepatocytes in vivo (see above!)
• Similarly, our friends from Homology Medicines have an update on producing monoclonal antibodies (delivered by AAV) in vivo to target C5 and its interaction with mouse FcRn in poster #365 and another poster on AAV integration in poster #164
• Another company working on producing mAbs in vivo: REGENXBIO presents an AAV8 vector expressing anti-pkal in WT mice, humanized mice, or NHP. They show that mAb concentrations were much lower in NHP or humanized mice compared to regular mice in poster #824
• So clearly, it is important to use a good AAV capsid for delivery to human hepatocytes and know that this might be different from delivery to mouse hepatocytes. This is shown again by Freeline using FRG mice in poster #122
• Previously, LK03 and KP1 AAV capsids were generated using FRG liver-humanized mice. These are now further being used in NHP studies, for example, by Dr. Kay’s group at Stanford to treat Factor IX in poster #699 and to understand the mechanism of transduction in poster #862
• Meanwhile, ASC Therapeutics will give an update on their second generation of AAV-based Gene Therapy for Hemophilia A in poster #783. Our model has been very useful for this research and allows them to move closer to clinical trials
• Our mice are not used just for AAV studies though. Sanofi and San Raffaele Telethon Institute are using a lentiviral vector to study Factor IX therapy in liver-humanized FRG mice in poster #358
• And Sana Biotechnology is using FRG mice to test Fusosome-Targeted Gene Transfer to Human Hepatocytes in poster #875. “We observed nearly 50% transduction of human hepatocytes in vivo“: INCREDIBLE!
• What else? our friends at Ambys Medicines are showing results from the FRG rat (sometimes a mouse is not big enough) in poster #386. They use these as bioreactors to amplify primary human hepatocytes since these don’t grow in vitro – congrats, Dr. Hickey!
• Even better, Ambys Medicines edit those hepatocytes to be universally acceptable by human recipients in poster #854. This could be a breakthrough to overcome liver donor shortages!
• The next step from Ambys Medicines: make those hepatocytes hyperfunctional by overexpressing a target that you lack, a small number of repopulated hepatocytes could help to reach physiological levels in the blood in poster #243.
• Learn about PASTE, the new drag and drop CRISPR-based genome insertion technology from Dr. Abudayyeh and Dr. Gootenberg at MIT in Ballroom A on 5/18 (9:15-9:40 am) during the Scientific Symposium.
• LogicBio will present how to save FRG mice without needing to transplant them, effectively using GeneRide to cure their HT1 in poster #537

In case you missed them, here are a couple recent publications that touch on the utility of liver-humanized FRG mice for gene therapy applications.