Hepatocytes, hematopoietic stem cells, B-cells and neurons
Many different cell types are important when dealing with genetic medicines. We have applied our RITDM technology to a number of human cell types that are important therapeutics targets to demonstrate that the RITDM platform has wide applicability. These cell types include hepatocytes, hematopoietic stem cells, B-cells and neurons
Hepatocytes are liver cells relevant for many metabolic diseases:
- Hepatocytes are metabolically very active and play important roles in detoxification and protein synthesis
- When certain genes are inactive in hepatocytes, this may impact the total body and can result in severe diseases
- Therapeutically liver cells are good targets, as they can be more easily reached and correcting genetic defects in the liver can have its impact throughout the body
Hematopoietic stem cells (HSCs) are the blood forming cells that are involved in many blood-borne and immunological features:
- Corrected genetic deficiencies in these stem cells can have a lifelong beneficial impact, as these cells are very long lived, and they are the precursors for blood cells and immune cells
- Genetic diseases that have their basis in HSCs include a wide spectrum of disease like Sickle Cell Disease, beta-Thalassemia, immune-deficiencies, lysosomal storage disorders etc.
B-cells have the following unique properties:
- B-cells can be easily isolated from PBMCs that are abundant when collecting blood samples from individuals
- B-cells are well suited for the production and secretion of proteins in the human body
- In the human body B-cells are long-lived and they can migrate to many different tissues and locations
We have developed an efficient ex vivo genome editing procedure that can be used in combination with our RITDM™ gene editing technology. B-cells can be developed to make proteins that can become the basis for new genetic medicines.
Neurons as brain cells can be involved in conditions that occur early and late in life:
- Neurons are non-dividing cells that are staying active throughout life
- Genetic mutations can result in conditions that manifest early in life (e.g. Huntington’s disease) or they can be a risk factor in develop chronic conditions later in life (e.g. Alzheimer’s disease)
- Converting disease causing mutations, but also changing mutations that elevate risk to neutral or protective variants is one of the outstanding aims for gene editing in general
The benefits of repeat dosing
Our RITDM gene editing technology has been further developed to make use of humanized components. This was done, amongst others, to minimize the chance for immunological reactions. Consequently, we have the potential to develop therapies in which patients can be treated more than once. For diseases that impact large numbers of cells (e.g. muscle diseases), cells that are difficult to reach (e.g. bone marrow stem cells) or tissues to renew cells (e.g. lungs) the ability to treat at multiple ages and stages is expected to provide better outcomes. It also provides the potential to treat severe diseases at an earlier stage and to perform follow on treatments as needed.