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The range of reproductive options investigated by the URPP H2R includes the potential future scenarios that rely on CRISPR-based technologies. The opportunities and risks of human germline editing using the CRISPR technology are being discussed extensively worldwide. Genetic modification of the germline with CRISPR might represent a promising approach for curing monogenetic disorders (e.g. cystic fibrosis), and for reducing genetic risk factors associated with common chronic diseases in which multiple genes interact with environmental factors (e.g. obesity, coronary heart disease, diabetes, Alzheimer’s disease, and multiple cancers). However, the consequences of such modifications for future generations are still unclear; indications are ambiguous, and technical feasibility is challenging. Here, we intend to evaluate opportunities, risks, and limitations specific to the CRISPR technology for germline editing. We will address these specific questions:
This high-risk sub-project unites competencies in biology, reproductive medicine, Artificial intelligence/machine learning, embryology, genetics, philosophy, theology, sociology, and law.
Our first goal is to assess the efficiency and precision of available CRISPR technologies and to develop improved variants.
Our second goal is therefore to evaluate the technical feasibility of introducing multiple precise genetic changes in a single cell or zygote.
Our third goal is to systematically introduce and study disease-associated allele variants in mouse models and ex vivo organoid models. Potential target diseases include cardiovascular diseases, obesity, and cancer.
In the first four years, we will mainly focus on testing the efficacy and safety of CRIPSR technologies, and in years 5 to 8 we will put an emphasis on the development of improved tools. Likewise, in the first four years, we will mainly try to understand why risk alleles are associated with certain genetic diseases, and in the years 5 to 8, we will attempt to develop CRISPR approaches that can correct mouse models carrying these risk alleles. Concurrent with this cutting-edge medical-technological research, we will conduct an interdisciplinary legal, ethical-
philosophical, psychological, and social investigation whose findings will inform the evaluation of CRISPR.
Transient in vivo prime editing for clinical applications
Eleonora Ioannidi’s PhD research project with Prof. Gerald Schwank “Transient in vivo prime editing for clinical applications” focuses on improving genome editing tools for their future use in gene therapy. Even though over the last few decades, genome editing technologies have been significantly improved, there are still challenges that need to be resolved prior their use for clinical applications such as their delivery and potential off targets. This project aims for making prime editing, a new technology that allows different modifications without causing double strand breaks, transient, while maintaining its precision and efficiency.
Applications of AI in the development of genome editing tools
Dr. Amina Mollaysa’s andProf. Michael Krauthammer’s research project "Applications of AI in the development of genome editing tools" addresses the following research questions:
The range of reproductive options investigated by the URPP H2R includes future scenarios that rely on CRISPR-based technologies. These investigations focus on the opportunities and risks of human germline editing tools that might represent a promising approach for curing monogenetic disorders (e.g. cystic fibrosis), and for reducing genetic risk factors associated with common chronic diseases in which multiple genes interact with environmental factors (e.g. obesity, coronary heart disease, diabetes, Alzheimer’s disease, and various cancers). However, the efficiency of germline modifications is still low, outcomes are unstable; indications are ambiguous, and technical feasibility is challenging. Given the complexities of the undertaking, the use of AI in the development of genome editing tools is warranted, with the goal of enabling more precise and controlled DNA modifications.
Ethical Issues of Germline Genome Editing from a Reproductive Justice Perspective
Agnes Kandlbinder’s PhD research project with Prof. Dr. Peter Schaber and Prof. Dr. Michael Coors “Ethical Issues of Germline Genome Editing from a Reproductive Justice Perspective” explores normative questions of Germline Genome Editing (GGE) at the intersection of applied ethics and societal debate. The cumulative dissertation critically examines both bioethical scholarship and activist discourses on GGE, particularly with regard to disability as a social justice issue. Thereby, the project aims to signpost how the public and academic discussion on research on GGE can be fruitfully brought forward in an inclusive way. Methodologically, Agnes combines tools of analytical applied ethics with a reproductive justice framework.
The expected duration of the project is from February 2022 to February 2025.