Data- and knowledge-derived functional landscape of human solute carriers DOI Creative Commons
Ulrich Goldmann, Tabea Wiedmer,

Andrea Garofoli

et al.

Molecular Systems Biology, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Abstract The human solute carrier (SLC) superfamily of ~460 membrane transporters remains the largest understudied protein family despite its therapeutic potential. To advance SLC research, we developed a comprehensive knowledgebase that integrates systematic multi-omics data sets with selected curated information from public sources. We annotated substrates through literature curation, compiled disease associations using mining techniques, and determined subcellular localization SLCs by combining annotations databases an immunofluorescence imaging approach. This SLC-centric knowledge is made accessible to scientific community via web portal featuring interactive dashboards visualization tools. Utilizing this systematically collected resource, computationally derived integrated functional landscape for entire superfamily. identified clusters distinct properties established distances between transporters. Based on all available their integration, assigned biochemical/biological functions each SLC, making study one gene function potential blueprint future research endeavors.

Language: Английский

Drug delivery systems for CRISPR-based genome editors DOI
Victoria J. Madigan, Feng Zhang, James E. Dahlman

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(11), P. 875 - 894

Published: Sept. 18, 2023

Language: Английский

Citations

80
Uncovering the functional diversity of rare CRISPR-Cas systems with deep terascale clustering DOI
Han Altae-Tran, Soumya Kannan,

Anthony J. Suberski

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6673)

Published: Nov. 23, 2023

Microbial systems underpin many biotechnologies, including CRISPR, but the exponential growth of sequence databases makes it difficult to find previously unidentified systems. In this work, we develop fast locality-sensitive hashing-based clustering (FLSHclust) algorithm, which performs deep on massive datasets in linearithmic time. We incorporated FLSHclust into a CRISPR discovery pipeline and identified 188 unreported CRISPR-linked gene modules, revealing additional biochemical functions coupled adaptive immunity. experimentally characterized three HNH nuclease-containing systems, first type IV system with specified interference mechanism, engineered them for genome editing. also candidate VII system, show acts RNA. This work opens new avenues harnessing broader exploration vast functional diversity microbial proteins.

Language: Английский

Citations

79
CRISPR technologies for genome, epigenome and transcriptome editing DOI
Lukas Villiger,

Julia Joung,

Luke W. Koblan

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(6), P. 464 - 487

Published: Feb. 2, 2024

Language: Английский

Citations

75
Genetics of human brain development DOI
Yi Zhou, Hongjun Song, Guo‐li Ming

et al.

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(1), P. 26 - 45

Published: July 28, 2023

Language: Английский

Citations

72
A host of armor: Prokaryotic immune strategies against mobile genetic elements DOI Creative Commons
David Mayo-Muñoz, Rafael Pinilla‐Redondo, Nils Birkholz

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(7), P. 112672 - 112672

Published: June 21, 2023

Prokaryotic adaptation is strongly influenced by the horizontal acquisition of beneficial traits via mobile genetic elements (MGEs), such as viruses/bacteriophages and plasmids. However, MGEs can also impose a fitness cost due to their often parasitic nature differing evolutionary trajectories. In response, prokaryotes have evolved diverse immune mechanisms against MGEs. Recently, our understanding abundance diversity prokaryotic systems has greatly expanded. These defense degrade invading material, inhibit genome replication, or trigger abortive infection, leading population protection. this review, we highlight these strategies, focusing on most recent discoveries. The study defenses not only sheds light microbial evolution but uncovers novel enzymatic activities with promising biotechnological applications.

Language: Английский

Citations

69
RNA‐based medicine: from molecular mechanisms to therapy DOI Creative Commons
Anke Sparmann, Jörg Vogel

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(21)

Published: Sept. 20, 2023

Abstract RNA‐based therapeutics have the potential to revolutionize treatment and prevention of human diseases. While early research faced setbacks, it established basis for breakthroughs in drug design that culminated extraordinarily fast development mRNA vaccines combat COVID‐19 pandemic. We now reached a pivotal moment where RNA medicines are poised make broad impact clinic. In this review, we present an overview different strategies generate novel therapeutics, including antisense RNAi‐based mechanisms, mRNA‐based approaches, CRISPR‐Cas‐mediated genome editing. Using three rare genetic diseases as examples, highlight opportunities, but also challenges wide‐ranging applications class drugs.

Language: Английский

Citations

59
Chemically Modified Platforms for Better RNA Therapeutics DOI

Yesi Shi,

Xueyan Zhen,

Yiming Zhang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(3), P. 929 - 1033

Published: Jan. 29, 2024

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential disease prevention and treatment. However, despite their remarkable achievements, these encounter substantial challenges including low stability, susceptibility to degradation by nucleases, prominent negative charge, thereby hindering further development. Chemically modified platforms emerged as strategic innovation, focusing on precise alterations either RNA moieties or associated delivery vectors. This comprehensive review delves into platforms, underscoring significance augmenting performance translational prospects of therapeutics. It encompasses an in-depth analysis various chemically that been instrumental propelling therapeutics toward clinical utility. Moreover, scrutinizes rationale behind diverse chemical modification techniques aiming at optimizing therapeutic efficacy molecules, facilitating robust management. Recent empirical studies corroborating enhancement through modifications are highlighted. Conclusively, we offer profound insights transformative impact drugs delineates prospective trajectories for future development integration.

Language: Английский

Citations

52
In vivo editing of lung stem cells for durable gene correction in mice DOI
Yehui Sun, Sumanta Chatterjee,

Xizhen Lian

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6701), P. 1196 - 1202

Published: June 13, 2024

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of in cells, yielding responses. Intravenously administered gene-editing LNPs activatable tdTomato mice achieved >70% lung editing, sustaining expression >80% epithelial cells 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X mediated >95% transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function primary patient-derived bronchial equivalent to Trikafta F508del, corrected intestinal organoids and R553X nonsense mutations 50% CF mice. These findings introduce LNP-enabled tissue disease-modifying correction.

Language: Английский

Citations

46
Collateral activity of the CRISPR/RfxCas13d system in human cells DOI Creative Commons
Peiguo Shi, Michael R. Murphy, Alexis O. Aparicio

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: March 28, 2023

Abstract CRISPR/Cas13 systems are increasingly used for programmable targeting of RNAs. While Cas13 nucleases capable degrading both target RNAs and bystander in vitro bacteria, initial studies fail to detect collateral degradation non-target eukaryotic cells. Here we show that RfxCas13d, also known as CasRx, a widely system, can cause transcriptome destruction when abundant reporter RNA endogenous RNAs, resulting proliferation defect these results call caution using RfxCas13d targeted knockdown, demonstrated the activity be harnessed selective depletion specific cell population defined by marker an setting.

Language: Английский

Citations

45
Application of CRISPR-Cas9 genome editing technology in various fields: A review DOI Creative Commons
Arif Nur Muhammad Ansori, Yulanda Antonius,

Raden JK. Susilo

et al.

Narra J, Journal Year: 2023, Volume and Issue: 3(2), P. e184 - e184

Published: Aug. 27, 2023

CRISPR-Cas9 has emerged as a revolutionary tool that enables precise and efficient modifications of the genetic material. This review provides comprehensive overview technology its applications in genome editing. We begin by describing fundamental principles technology, explaining how system utilizes single guide RNA (sgRNA) to direct Cas9 nuclease specific DNA sequences genome, resulting targeted double-stranded breaks. In this review, we provide in-depth explorations agriculture, medicine, environmental sciences, fisheries, nanotechnology, bioinformatics, biotechnology. also highlight potential, ongoing research, ethical considerations controversies surrounding use. might contribute understanding implications various fields, paving way for future developments responsible transformative technology.

Language: Английский

Citations

44