Category: News

To study the impact of epigenomic changes in functional genomics, it is essential to unravel the complex cellular processes that control chromatin state and activity. Lei Qi and colleagues provide a comprehensive overview of available CRISPR tools to investigate epigenetic modifications and the functional consequences.

For more information, see:
Nakamura, M., Gao, Y., Dominguez, A.A, Qi, L.S. (2021) CRISPR technologies for precise epigenome editing. Nat. Cell Biol. 23, 11–22. https://doi.org/10.1038/s41556-020-00620-7

Questions? Email: crispr@amsterdamumc.nl

Members of the David Liu lab published an exciting manuscript in Nature underlining the potential of CRISPR base editors to treat human genetic diseases. They use an adenine base editor to correct a dominant-negative mutation in LMNA that causes the premature aging disease Hutchinson–Gilford progeria syndrome (HGPS). After providing proof of principle based on cell culture experiments, the authors applied adeno-associated virus 9 to deliver their base editor in vivo in a mouse model of HGPS. After a single injection of the modified virus, long lasting correction of the pathogenic mutation was observed in various organs with efficiencies ranging from 20-60%. Importantly, the vitality and life-span of the treated mice greatly increased.

For more information, see:
Koblan et al. (2021) In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice. Nature. https://doi.org/10.1038/s41586-020-03086-7

Keywords: CRISPR, Base Editor, Hutchinson–Gilford progeria syndrome

Questions? Email: crispr@amsterdamumc.nl

Consult this guide when you plan your CRISPR experiments

Addgene released the third edition of their CRISPR 101 ebook. The book provides a clear and comprehensive overview of numerous CRISPR research applications and available tools. This desktop resource is free of charge and a must-have for any contemporary scientist in molecular biology.

Get your free copy here: https://www.addgene.org/educational-resources/ebooks/

Keywords: CRISPR, Methods, Tools, Addgene

Questions? Email: crispr@amsterdamumc.nl

Bacterial retrons were originally discovered in 1984 as abundant multicopy single stranded DNA molecules. The DNA molecule is the product of a reverse transcriptase based on a non-coding RNA template. The name retron is derived from its reverse transcriptase, however, the DNA-RNA hybrid structure is also an integral part of the complex. So far, the function of retrons has remained enigmatic. Now, two research groups independently identified that retrons are part of the bacterial defense system against phage infections. Retrons initiate cell death in individual bacteria upon phage entry, providing a protective effect on the population. Retron activity has only been documented in bacteria and gene editing potential in eukaryotic cells has yet to be explored.    

For more information, see:
Millman et al. (2020) Bacterial retrons function in anti-phage defense. Cell https://doi.org/10.1016/j.cell.2020.09.065
Bobonis et al. (2020) Phage proteins block and trigger retron toxin/antitoxin systems. BioRxiv https://doi.org/10.1101/2020.06.22.160242
Penissi (2020) Like CRISPR, mystery gene editor began as a virus fighter. Science DOI: 10.1126/science.370.6519.898

Keywords: CRISPR, bacterial immune system, phage, retron

Questions? Email: crispr@amsterdamumc.nl

The direct application of CRISPR gene editing against tumors has shown promise but in vivo delivery issues have hampered therapeutic development. In a ground-breaking study, Rosenblum et al. applied antibody-guided lipid nanoparticles to deliver mRNA which encoded gene editing tools to disrupt the polo-like kinase 1 (PLK1) gene, resulting in mitotic arrest and apoptosis. The efficacy of this novel cancer therapy was monitored in mouse models with glioblastoma and ovarian adenocarcinoma. Following the in vivo cancer targeting and gene editing, the authors observed CRISPR activity in 70 – 80% of the tumor cells, associated with a specific induction of apoptosis, reduced cancer growth and the prolonged survival of treated mice.

For more information, see:
Rosenblum et al. (2020) CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy. Science Adv. DOI: 10.1126/sciadv.abc9450

Keywords: CRISPR, cancer treatment, lipid nanoparticles

Questions? Email: crispr@amsterdamumc.nl

Natalie Kofler is the founding director of ‘Editing Nature’, a platform to support responsible decisions about genetic engineering. She published a review of the book ‘Editing Humanity’ by Kevin Davies, executive editor of The CRISPR Journal.

For more information, see: https://www.nature.com/articles/d41586-020-03071-0

Keywords: CRISPR, Ethics, Society, Book Review

Questions? Email: crispr@amsterdamumc.nl

From the lab of Jürgen Knoblich at the Institute of Molecular Biotechnology, Vienna, Science has published a CRISPR loss of function (LOF) screen in human cerebral organoids. By combining cell-barcoding with CRISPR-cell lineage tracing the authors were able to distinguish loss of proliferation following gRNA-mediated gene disruption from cell growth variability in 3D culture systems.

Reference: Esk C., Lindenhofer D., Haendeler S., Wester R.A., Pflug F., Schroeder B., Bagley J.A., Elling U., Zuber J., von Haeseler A., Knoblich J.A. (2020) A human tissue screen identifies a regulator of ER secretion as a brain size determinant. Science. DOI: 10.1126/science.abb5390.

Keywords: CRISPR LOF screen, Barcodes, Lineage Tracing, 3D Culture

For more information: https://www.kva.se/en/pressrum/pressmeddelanden/nobelpriset-i-kemi-2020

Keywords: CRISPR, Cas9, Nobel Prize

Carlson-Stevermer et al. incorporate photocleavable residues in sgRNAs enabling inactivation upon exposure to UV light. CRISPRoff provides spatial and temporal control of gene editing activities.

Reference: Carlson-Stevermer, J., Kelso, R., Kadina, A. et al. (2020) CRISPRoff enables spatio-temporal control of CRISPR editing. Nat. Commun. 11, 5041. https://doi.org/10.1038/s41467-020-18853-3

Keywords: CRISPRoff, sgRNA cleavage, Spatio-Temporal control

Questions? Email: crispr@amsterdamumc.nl

From the lab of Jason Moffat, Nature has published a study in which the mouse (m)TKO whole genome CRISPR library is used to identify genes that support tumor cells to escape from cytotoxic T lymphocytes. 

Reference: Lawson, K.A., Sousa, C.M., Zhang, X. et al. (2020) Functional genomic landscape of cancer-intrinsic evasion of killing by T cells. Nature 586, 120–126. https://doi.org/10.1038/s41586-020-2746-2

Keywords: CRISPR screen, Cancer, Cytotoxic T cells, Immune Evasion

Questions? Email: crispr@amsterdamumc.nl