Dilated cardiomyopathies (DCM) are heart diseases whose prognosis is worse than many types of cancer. The heart muscle sags and loses more and more of its strength as a result. One of its particularly aggressive forms is triggered by mutations of the gene LMNA. Repairing the mutation is the only way to deal with the cause. Julian Grünewald plans to correct these mutations with the help of prime editors.
"With great initiative and creativity, Julian Grünewald has made important contributions to the progress of gene editing," says Prof. Werner Müller-Esterl, chairman of the Life Sciences Bridge Award jury. "His current projects demonstrate courage and strategic clarity. Grünewald is now looking for ways to use prime editors to address severe genetic heart disease in a temporary tenure-track professorship in cardiology at TUM's clinic. We want to use this award to help him cross the bridge to a tenured professorship."
So far, the liver has been the preferred target organ of therapeutic gene editing. "The cardiac muscle cell is a special challenge," says Grünewald. Unlike liver cells, which regenerated incessantly, cardiac muscle cells remained the same throughout their lives, placing the highest demands on their integrity at the DNA level.
Grünewald learned his trade in one of the world's leading gene editing laboratories in Boston. There, he made significant contributions to base editing optimisation. As a post-doctoral fellow in Prof. J. Keith Joung's lab at Massachusetts General Hospital, he optimised CRISPR nucleases, base editors, and prime editors for nearly five years since 2017.
Unlike the CRISPR-Cas process from which they are derived, these gene editors cut only one strand of genetic information DNA, rather than the double helix. This makes their handling exceptionally safe.
Original puplication:
Hsu, J.Y., Grünewald, J. et al. - PrimeDesign software for rapid and simplified design of prime editing guide RNAs. Nature Communications 12, 1034 (2021) doi.org/10.1038/s41467-021-21337-7
Grünewald, J. et al. - CRISPR DNA base editors with reduced RNA off-target and self-editing activities. Nature Biotechnology, 37(9), 1041–1048 (2019) doi.org/10.1038/s41587-019-0236-6
Grünewald, J. et al. Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature, 569(7756), 433–437 (2019) doi.org/10.1038/s41586-019-1161-z https://doi.org/10.1038/s41586-019-1161-z
