Research

The Ultimate Goals of GCTL

1. To alleviate suffering by accelerating the application of advanced technologies, thereby reducing pain for those in need. 

2. To contribute to the advancement of fundamental scientific knowledge and understanding

1. Unraveling Genotoxic Mechanisms Induced by Gene Editing and Advancing Next-Generation Gene and Cell Therapies 

Elucidating the Mechanisms of Genotoxicity Mediated by Precision Gene Editing 

• Molecular and cellular analysis of the DNA damage repair pathway, including the p53 superfamily, in hematopoietic stem cells following gene editing via CRISPR/Cas9-NHEJ knockout, CRISPR/Cas9-HDR knock-in, as well as next-generation gene editing techniques such as base-editing for single base conversion and PRIME editing.

• Research on improving engraftment ability by inhibiting mechanisms of genotoxicity : Prediction and tracking of hematopoiesis in vivo and in vitro in hematopoietic stem cells treated with genotoxicity inhibitors. 

Development of Bone Marrow Organoid as an Alternative Model to Hematopoietic Stem Cell Transplantation 

• Construction of bone marrow organoids that replicate bone marrow structures using an established protocol and iPSCs with enhanced osteogenic differentiation capability.

• Verification of the presence and function of stromal cells, lumen-forming vasculature, and hematopoietic cells, as well as the reproduction of osteoid lineage. Additionally, examination of differentiation into lymphoid cells, smooth muscle cells, and adipocytes.

• Transplantation of hematopoietic stem cells into bone marrow organoids to analyze the interactions between bone marrow constituent cells and hematopoietic stem cells, as well as the initial engraftment mechanisms.

Verification of the Efficacy of in vivo Gene Therapy by using Lipid Nanoparticles 

• Apply gene editors via lipid nanoparticles to verify the efficiency of genetic material delivery and the effective delivery of packed genotoxicity suppression candidate substances. 

• Set an ex vivo gene therapy model as a control group and conduct comparative studies with current gene therapy application methods. 

• Verify the results derived from bone marrow organoids through comparative studies in animal models. 

2. Enhancement of the Therapeutic Ability of Mesenchymal Stem Cells against the Immune-mediated Disorders through Disease-specific Pretreatment 

Augmentation of Immunomodulatory Function of Mesenchymal Stem Cells by Disease-specific licensing

• Verify the regulatory ability of enhanced function MSCs on Th1/17 cell differentiation and major cytokine production.

• Analyze the regulatory ability of enhanced function MSCs on the secretion of Th1/17 cell-related cytokines.

Verification of Intestinal Integrity and Anti-Inflammatory Effects

• Study the restoration of permeability in intestinal epithelial cells through co-culture with enhanced function stem cells by assessing the expression of tight junction proteins  or adherens junction proteins .

• Determine the anti-inflammatory effects on intestinal epithelial cells after co-culturing with licensed MSCs by analyzing pro-inflammatory cytokines such as IL-6, IL-8, IL-1β, and IL-17C.