Gene Editing
The Gene Editing Group is dedicated to discovering, developing, and applying innovative genetic tools that drive translational advances in cell and gene therapies. We work with promising systems such as CRISPR/Cas9, CRISPRi, and Cas13d, which require specific adaptations for each unique application. Our research addresses critical challenges in areas like gene therapy (Moretti et al., 2020), cell replacement therapies (Giehrl-Schwab et al., 2022), and novel RNA modulation and imaging systems (Gruber et al., 2024). For therapies that target specific cell types such as stem cells, or cells in challenging environments like the CNS, precise, targeted delivery is essential. To meet this need, we are developing a novel delivery platform inspired by nature, enhanced by artificial intelligence, and built with synthetic proteins (Schuhmacher et al., submitted). In addition, our transgenic unit supports both in-house scientists and external collaborators by creating customized model systems, including iPSCs and advanced mouse models (Giusti et al., 2024; Behrens et al., 2021). Overall, our vision is to empower the next generation of scientific and translational breakthroughs by providing and applying tailored genetic tools.
The Gene Editing Group is dedicated to discovering, developing, and applying innovative genetic tools that drive translational advances in cell and gene therapies. We work with promising systems such as CRISPR/Cas9, CRISPRi, and Cas13d, which require specific adaptations for each unique application. Our research addresses critical challenges in areas like gene therapy (Moretti et al., 2020), cell replacement therapies (Giehrl-Schwab et al., 2022), and novel RNA modulation and imaging systems (Gruber et al., 2024). For therapies that target specific cell types such as stem cells, or cells in challenging environments like the CNS, precise, targeted delivery is essential. To meet this need, we are developing a novel delivery platform inspired by nature, enhanced by artificial intelligence, and built with synthetic proteins (Schuhmacher et al., submitted). In addition, our transgenic unit supports both in-house scientists and external collaborators by creating customized model systems, including iPSCs and advanced mouse models (Giusti et al., 2024; Behrens et al., 2021). Overall, our vision is to empower the next generation of scientific and translational breakthroughs by providing and applying tailored genetic tools.
Publications
2024 Nature Communications Nat. Commun. 15:6632 (2024)
Correction to "The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3'-UTR and promoting Rag1 mRNA expression".
2024 Scientific Article in Cell Discovery Cell Discov. 10:42 (2024)
Engineered, nucleocytoplasmic shuttling Cas13d enables highly efficient cytosolic RNA targeting.
2024 Scientific Article in Science Advances Sci. Adv. 10:eadj8769 (2024)
A brain-enriched circular RNA controls excitatory neurotransmission and restricts sensitivity to aversive stimuli.
2024 Scientific Article in Neurobiology of Disease Neurobiol. Dis. 194:106474 (2024)
Engrailed 1 deficiency induces changes in ciliogenesis during human neuronal differentiation.
2024 Scientific Article in Nature Communications Nat. Commun. 15:2194 (2024)
The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3'-UTR and promoting Rag1 mRNA expression.
2023 Scientific Article in Proceedings of the National Academy of Sciences of the United States of America Proc. Natl. Acad. Sci. U.S.A. 120, 11:e2309205120 (2023)
Unrestrained cleavage of Roquin-1 by MALT1 induces spontaneous T cell activation and the development of autoimmunity.
2023 Scientific Article in Nature Communications Nat. Commun. 14:7674 (2023)
A reversible state of hypometabolism in a human cellular model of sporadic Parkinson's disease.
2023 Scientific Article in Experimental Eye Research Exp. Eye Res. 226:109346 (2023)
Identification of ocular regulatory functions of core histone variant H3.2.
2022 Scientific Article in Scientific Reports Sci. Rep. 12:21951 (2022)
Toxicity of extracellular alpha-synuclein is independent of intracellular alpha-synuclein.
2022 Scientific Article in Nature Communications Nat. Commun. 13:4819 (2022)
Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease.
2022 Scientific Article in Nature Cardiovascular Research Nat. Cardio. Res. 1, 157-173 (2022)
Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy.
2022 Scientific Article in EMBO Molecular Medicine EMBO Mol. Med.:e14797 (2022)
Parkinson's disease motor symptoms rescue by CRISPRa-reprogramming astrocytes into GABAergic neurons.
2021 Scientific Article in Nature Immunology Nat. Immunol. 22, 1563-1576 (2021)
Disrupting Roquin-1 interaction with Regnase-1 induces autoimmunity and enhances antitumor responses.
2021 Other: Opinion in Brain: A Journal of Neurology Brain 144, 3555-3557 (2021)
c-Abl phosphorylation primes PARIS for neurodegeneration.
2021 Scientific Article in Science immunology Sci. Immunol. 6:eabh2095 (2021)
TRAF6 prevents fatal inflammation by homeostatic suppression of MALT1 protease.
2021 Scientific Article in Nature Cell Biology Nat. Cell Biol. 23, 652-663 (2021)
Non-invasive and high-throughput interrogation of exon-specific isoform expression.
2021 Scientific Article in The CRISPR Journal CRISPR J. 4, 178-190 (2021)
Rescue of STAT3 function in hyper-IgE syndrome using adenine base editing.
2021 Scientific Article in Blood Blood 137, 1932-1944 (2021)
Mammalian VPS45 orchestrates trafficking through the endosomal system.
2021 Scientific Article in PLoS Genetics PLoS Genet. 16:e1009190 (2021)
Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.
2021 Scientific Article in Cell Stem Cell Cell Stem Cell 28, 524-534.e7 (2021)
CRISPR-mediated induction of neuron-enriched mitochondrial proteins boosts direct glia-to-neuron conversion.
2020 Scientific Article in Science Translational Medicine Sci. Transl. Med. 12:eaau3960 (2020)
A patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson's disease.
2020 Scientific Article in Journal of Clinical Investigation J. Clin. Invest. 130, 6093-6108 (2020)
Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity.
2020 Scientific Article in Nature medicine Nat. Med. 26, 207-214 (2020)
Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy.
2020 Scientific Article in Nature Communications Nat. Commun. 11:655 (2020)
Human and mouse essentiality screens as a resource for disease gene discovery.
2019 Meeting abstract in Investigative Ophthalmology & Visual Science, IOVS Invest. Ophthalmol. Vis. Sci. 60 (2019)
Identification of ocular regulatory functions of core histone variant H3.2 in mouse.
2019 Scientific Article in Experimental Eye Research Exp. Eye Res. 188:107632 (2019)
Mutation in the mouse histone gene Hist2h3c1 leads to degeneration of the lens vesicle and severe microphthalmia.
2019 Scientific Article in Scientific Reports Sci. Rep. 9:4515 (2019)
The Parkinson's disease-linked Leucine-rich repeat kinase 2 (LRRK2) is required for insulin-stimulated translocation of GLUT4.
2018 Scientific Article in Journal of Chromatography A J. Chromatogr. A 1534, 85-92 (2018)
Determination of thyroid hormones in placenta using isotope-dilution liquid chromatography quadrupole time-of-flight mass spectrometry.
2017 Scientific Article in Nature Communications Nat. Commun. 8:886 (2017)
A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction.
2017 Scientific Article in Disease Models and Mechanisms Dis. Model. Mech. 10, 981-991 (2017)
Meis1 effects on motor phenotypes and the sensorimotor system in mice.
2017 Scientific Article in Neurobiology of Disease Neurobiol. Dis. 105, 179-193 (2017)
The pathogenic LRRK2 R1441C mutation induces specific deficits modeling the prodromal phase of Parkinson's disease in the mouse.
2017 Scientific Article in Neuroscience Neuroscience 357, 241-254 (2017)
Alterations in neuronal control of body weight and anxiety behavior by glutathione peroxidase 4 deficiency.
2017 Scientific Article in Journal of Neuroscience Methods J. Neurosci. Methods, DOI: 10.1016/j.jneumeth.2017.05.005 (2017)
Analysis of locomotor behavior in the German Mouse Clinic.
2016 Scientific Article in Journal of Chromatography J. Chromatogr. B 1033-1034, 413-420 (2016)
Determination of thyroid hormones in mouse tissues by isotope-dilution microflow liquid chromatography-mass spectrometry method.
2016 Review in Journal of Neurochemistry J. Neurochem. 139, 8-26 (2016)
Diversity matters - heterogeneity of dopaminergic neurons in the ventral mesencephalon and its relation to Parkinson's disease.
2016 Scientific Article in Hippocampus Hippocampus 26, 1250-1264 (2016)
Beware of your Cre-Ation: lacZ expression impairs neuronal integrity and hippocampus-dependent memory.
2016 Scientific Article in Neurobiology of Disease Neurobiol. Dis. 89, 112-125 (2016)
Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism.
2014 Scientific Article in PLoS ONE PLoS ONE 9:e101124 (2014)
FGF/FGFR2 signaling regulates the generation and correct positioning of Bergmann glia cells in the developing mouse cerebellum.
2014 Scientific Article in Molecular and Cellular Biology Mol. Cell. Biol. 34, 2147-2161 (2014)
Leucine-rich repeat kinase 2 binds to neuronal vesicles through protein interactions mediated by its C-terminal WD40 domain.
2014 Scientific Article in Genome Research Genome Res. 24, 592-603 (2014)
Restless Legs Syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon.
2014 Scientific Article in Molecular and Cellular Proteomics Mol. Cell. Proteomics 13, 733-748 (2014)
A cell surface biotinylation assay to reveal membrane-associated neuronal cues: Negr1 regulates dendritic arborization.
2013 Scientific Article in Biochimica et Biophysica Acta - Molecular Basis of Disease Biochim. Biophys. Acta-Mol. Basis Dis. 1832, 2352-2367 (2013)
LRRK2 guides the actin cytoskeleton at growth cones together with ARHGEF7 and Tropomyosin 4.
2013 Scientific Article in PLoS ONE PLoS ONE 8:e63778 (2013)
Expression analysis of lrrk1, lrrk2 and lrrk2 splice variants in mice.
München, Technische Universität, Fakultät Wissenschaftszentrum Weihenstephan, Diss., 2012, 216 S.
Pathogenic mutation of Lrrk2 - a Mouse Model for pre-motor Parkinson’s disease.
2012 Scientific Article in Experimental Neurology Exp. Neurol. 235, 214-227 (2012)
Pink1-deficiency in mice impairs gait, olfaction and serotonergic innervation of the olfactory bulb.
2011 Scientific Article in Journal of Neuroscience J. Neurosci. 31, 2225-2237 (2011)
LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool.
2010 Scientific Article in BMC Neuroscience BMC Neurosci. 11, 158 (2010)
A powerful transgenic tool for fate mapping and functional analysis of newly generated neurons.
2010 Scientific Article in Genes, Brain and Behavior Genes Brain Behav. 9, 305-317 (2010)
DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area and exhibit non-motoric behavioural impairments.
München, Technische Universität, Fakultät für Biologie, Diplom-Arbeit, 2005