CRISPR Solutions Designed to Elevate Your Research

What inspired you to get into science and research? What inspires you to get up every day?

Curiosity about how my surroundings and living things work; I love the excitement of carrying out experiments, the anticipation for results, and the fulfillment of knowing that I am contributing to the development of new medical treatments.

What drives your passion for science?

Knowing that I am working with cutting-edge technologies to develop therapies that will become available to patients in the next 5 to 10 years.

Can you provide an overview of your research?

Our goal is to treat hereditary diseases by correcting the underlying mutation in bone marrow stem cells so that these cells will be curative after they are transplanted back to the affected patient. The correction of mutations can be done by means of non-infectious viral vectors or more recently with nucleases that target specific sites in DNA, also known as molecular scissors (such as CRISPR-Cas9). Our laboratory covers a wide range of research, spanning basic science all the way to clinical studies; examples of diseases we work on are blood disorders (sickle cell anemia), severe combined immunodeficiency, and Fanconi anemia (defects in DNA repair).

What are the current challenges you face?

One challenge is to correct mutations and engineer DNA in bone marrow stem cells with high efficiency and without affecting the identity of these cells so that they will differentiate into all blood cell types and reconstitute the hematopoietic system of a patient after transplantation. Another big challenge is in the scale-up, where we are looking to engineer the DNA of several hundred millions of cells obtained from patients.

What are the potential solutions?

One solution is to find a nuclease platform (such as CRISPR-Cas9) and nuclease delivery method (such as electroporation) that can treat large numbers of cells with minimum toxicity and high efficiency so that they will be therapeutic after they repopulate the patient. Another solution is to refine our definition of true, long-term hematopoietic stem cells, which will decrease the number of these cells that need to be treated.

Describe your results, if you have any.

We have so far done two transplant experiments in a preclinical animal model aimed at treating hemoglobinopathies (blood disorders). The results are very encouraging, but we want to follow up on our treatment for over a year to really understand how effective and safe our therapy is.

How are the advances in genome editing enabling you to achieve your research goals?

Current gene editing technologies allow us to target virtually any site in the genome in pretty much any cell type. In addition, the improved efficacy of TrueCut Cas9 Protein v2 allows us to reduce the amount used and minimize toxicity.

How are the tools and technologies today allowing you to lead to discovery?

Improved efficacy and safety of technology equals more potential to bring an effective therapy to the patient. These reagents are also available in large-scale [quantities] and in cGMP-grade for easy translation to the clinic.

What thought do you want to leave us with?

I am lucky to be working in such an exciting field with lots of potential to cure a variety of diseases. Nevertheless, researchers need to be vigilant to take all necessary steps to not move this approach too quickly to the patient to avoid any major setbacks.