APPLICATION — GENE & CELL THERAPY
Validate Your Approach with Human Relevance.
A complete platform from in vitro development & optimization to in vivo validation
Uses of FRG® KO Models in Gene Editing Applications
Gene editing technologies have evolved rapidly over the last decade, yet drug developers are struggling to advance programs to market. Designing gene delivery vehicles using traditional rodent models translates poorly to the clinic because these models lack human relevance. Liver-humanized FRG® KO animal models provide a new toolset for researchers in this space by allowing optimization, verification of target specificity, and evaluation of off-target effects in a human relevant setting. When speed and accuracy are critical to your program’s success, Yecuris in vitro and in vivo technologies are there to bridge the gap between bench and clinic.
Correction of humanized OTC FRG® KO Mouse model using ex vivo gene editing of human hepatocytes
FRG® KO Platform Advantage is a complete system to:
- Screen & optimize your delivery vehicle and/or payload in vitro using HepaCur™ freshly isolated or cryopreserved human hepatocytes
- Validate your leads in vivo with liver-humanized FRG® KO mouse models
- Use our custom transplant service to create animals with hepatocytes of your choice:
- any species (human, non-human primate, pig, rat, etc.)
- any genotypically defined donor (PNPLA3, GSD, OTC, MSUD, etc.)
- any donor of your choice
Target — are you hitting your specific target?
Test your selectivity & specificity with human relevance.
Payload — is your construct delivered?
Validate delivery of your payload into target cells.
Function — is your approach working?
Test your function
with precision.
Yecuris Custom Services
Full Cycle In Vitro → In Vivo Platform
Our gene editing platform begins with our primary human hepatocytes isolated from chimeric animals to optimize all of the conditions necessary including confirmation of donor specific human hepatocyte targeting and MOI optimization. Once these parameters are optimized, Yecuris uses the same donor hepatocytes in the FRG® KO mice to validate In Vivo targeting as well as any off-target effects of the treatment.
Ex Vivo Editing → In Vivo Model Generation
Identifying donors with highly specific mutations can be highly challenging, particularly in the case of rare mutations. An alternative approach to cell sourcing is to complete Ex Vivo editing of primary hepatocytes followed by subsequent transplantation of the edited cells into FRG® KO mice to create an In Vivo model of the disease. This model can then be utilized in combination with a therapeutic gene editing technology to reverse the engineered mutation in primary cells.
In Vivo Assessment of Liver Targeting
Assessment of gene targeting efficiency has proved to be a challenging technical issue for many programs. The FRG® KO mouse model can be used to optimize, validate, and quantify human specific targeting of your vector. Additionally, analysis can be performed to understand any off-target effects that the vector may present in other cell types and tissues.
Assessment of Selectivity & Specificity of Vector Delivery
Assessment of gene targeting efficiency has proved to be a challenging technical issue for many programs. The FRG® KO mouse model can be used to optimize, validate, and quantify human specific targeting of your vector. Additionally, analysis can be performed to understand any off-target effects that the vector may present in other cell types and tissues.
Screening & Optimization of Delivery Systems
With so many methods available for gene editing, choosing the optimal solution for your target can be challenging. Using Yecuris FRG® technologies can aid in your selection by screening your list of options to optimize for editing with human relevance while minimizing the off-target effects.
Serotype Screening Platform
Looking to screen your own viral serotypes? The FRG® KO mouse has been used as the premier platform for development and selection of AAV serotypes that are being used therapeutically today. You can learn more about the methods and procedures here.
Viral & Non-Viral Dosing
Yecuris study teams are well versed in both viral and non-viral methods of gene therapy administration. With hundreds of studies under our belt, over ten years of FRG® KO mouse experience, and a deep scientific bench, our teams are here to enable your next great breakthrough.
Isolation of Gene Edited Hepatocytes
After treatment with your vector therapy, Yecuris has full capabilities to isolate and process your gene edited hepatocytes for analysis or direct evaluation by In Vitro assays. We have developed processes for optimal isolation of the propagated hepatocytes with subsequent negative bead-based purification to remove residual mouse cells. Our process yields cell products that are over 98% pure with the ability to be shipped in suspension, plated as fresh, or cryopreserved for future work.
Custom Hepatocyte Transplantation
Yecuris offers custom hepatocyte transplantation with any donor that you require, from any species. Click here to learn more.
Tissue Harvesting and Preparation
For studies that require terminal endpoints, Yecuris can harvest and prepare tissues as formalin fixed, OCT embedded, or flash frozen in liquid nitrogen.
