Biology subjects

Kip, M.

Publications and source records attributed to Kip, M..

3 recordsLinked to original sources

bioRxiv2025

PROTAC molecule-mediated SpCas9 protein degradation for precise genome editing

CRISPR (clustered regularly interspaced short palindromic repeats) technology has revolutionized both fundamental research and genomic medicine. The need for precise control of SpCas9-based CRISPR genome editing has led to the development of various strategies to regulate Cas9 activity, aiming to minimize off-target effects. Proteolysis-targeting chimeras (PROTACs) use the ubiquitin-proteasome system to selectively degrade target proteins. Here, we developed CASPROTAC 6, a reversible and cell-permeable PROTAC degrader that directly targets SpCas9 proteins for degradation. The CASPROTAC 6 molecule was derived by linking a known SpCas9 binder BRD7087 with an S-substituted Lenalidomide cereblon (CRBN) ligand via a six-carbon alkyl linker. Our data show that CASPROTAC 6 is a broad-spectrum degrader of SpCas9 and variants such as dCas9 and Cas9 nickases. CASPROTAC 6 degrades SpCas9 and the SpCas9-guide RNA complex via the proteasome system by approximately 50%. As a result, CASPROTAC 6 effectively enhanced the precision of CRISPR/Cas9-mediated genome editing by increasing target specificity. CASPROTAC 6 may serve as modulators of CRISPR/SpCas9-associated nucleases, enabling precise genome editing while reducing off-target effects and enhancing biosafety.

biochemistry↗

bioRxiv2020

ODDPub - a Text-Mining Algorithm to Detect Data Sharing in Biomedical Publications

Open research data are increasingly recognized as a quality indicator and an important resource to increase transparency, robustness and collaboration in science. However, no standardized way of reporting Open Data in publications exists, making it difficult to find shared datasets and assess the prevalence of Open Data in an automated fashion.We developed ODDPub (Open Data Detection in Publications), a text-mining algorithm that screens biomedical publications and detects cases of Open Data. Using English-language original research publications from a single biomedical research institution (n=8689) and randomly selected from PubMed (n=1500) we iteratively developed a set of derived keyword categories. ODDPub can detect data sharing through field-specific repositories, general-purpose repositories or the supplement. Additionally, it can detect shared analysis code (Open Code).To validate ODDPub, we manually screened 792 publications randomly selected from PubMed. On this validation dataset, our algorithm detected Open Data publications with a sensitivity of 0.74 and specificity of 0.97. Open Data was detected for 11.5% (n=91) of publications. Open Code was detected for 1.4% (n=11) of publications with a sensitivity of 0.73 and specificity of 1.00. We compared our results to the linked datasets found in the databases PubMed and Web of Science.Our algorithm can automatically screen large numbers of publications for Open Data. It can thus be used to assess Open Data sharing rates on the level of subject areas, journals, or institutions. It can also identify individual Open Data publications in a larger publication corpus. ODDPub is published as an R package on GitHub.Competing Interest StatementThe authors have declared no competing interest.View Full Text

scientific communication and education↗

bioRxiv2019

Polar-like trophoblast stem cells form an embryonic-abembryonic axis in blastoids.

The early mammalian conceptus (blastocyst) comprises an outer trophoblast globe that forms an axis originating from the inner embryonic cells. From the mouse conceptus, Trophoblast stem cells (TSCs) are derived, which are in vitro analogues of early trophoblasts. Here, we show that TSCs contain plastic subpopulations reflecting developmental states ranging from pre- to post-implantation trophoblasts. However, upon exposure to a specific combination of embryonic inductive signals, TSCs globally acquire properties of pre-implantation polar trophoblasts (gene expression, self-renewal) juxtaposing the inner embryonic cells, and an enhanced, homogeneous epithelial phenotype. These lines of polar-like TSCs (pTSCs) represent a transcriptionally earlier state that more efficiently forms blastoids, whose inner embryonic cells then induce the patterning of gene expression along the embryonic-abembryonic axis. Altogether, delineating the requirements and properties of polar trophoblasts and blastocyst axis formation in vitro provides a foundation for the precise description and dissection of early development.

developmental biology↗