Gene editing technology and preclinical studies using animal models are indispensable for the clinical development of new therapeutics with increased efficacy and safety. It is critical to achieve high and reliable translatability from preclinical research to clinical development. Consistent with this, the need for humanized mouse models both in-vivo and in-vitro has increased substantially in recent years. Humanization enables animals to recapitulate disease mechanisms and report drug responses as if they were human patients.
Humanization can be accomplished in two ways:
- Genetically engineering the mouse model to express human genes and proteins
- Xenotransplantation and sustained livelihood of human tissue in the recipient model organism
Recent advancements in gene editing technology, especially CRISPR-Cas9, has enabled genetic engineering of essentially all living organisms at unprecedented speed and capacity. Taking advantage of this, GemPharmatech has generated more than ninety humanized mouse strains for the study of disease mechanisms and preclinical evaluation. Similarly, multiple syngeneic mouse tumor cell lines have been engineered to express human target genes, which complement the ever-growing portfolio of humanized mouse models for preclinical evaluation of immunotherapeutic reagents.
Successful xenotransplantation requires the use of immunodeficient recipients, which provides the permissive living environment needed to support the engraftment. With the advanced gene editing technology, GemPharmatech has generated a unique portfolio of severe immunodeficient mouse models, some of which are capable of sustaining the human xenograph for 86 weeks (about 1 and a half years) post-engraftment. To date, these animals have been used in three major applications: receiving non-self (human) engraftment, human immune system reconstitution using human PBMC (peripheral blood mononuclear cells) or human HSCs (hematopoietic stem cells), and human liver reconstitution using primary human hepatocytes post liver damage.