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

An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants DOI Creative Commons
Zhiqiang Duan,

Yafeng Liang,

Jialei Sun

et al.

The Innovation, Journal Year: 2024, Volume and Issue: 5(2), P. 100564 - 100564

Published: Jan. 8, 2024

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3. As a result, developed Cas-SF01, Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells. Cas-SF01 shows comparable or superior performance compared SpCas9 other Cas12 nucleases. Compared Cas12i3, has expanded PAM range effectively recognizes NTTN noncanonical NATN TTVN PAMs. In addition, identified amino acid substitution, D876R, markedly reduced the off-target effect while maintaining high on-target activity, leading development

Language: Английский

Citations

18

Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy DOI Creative Commons
Tao Lei, Yazhuo Wang, Yuchen Zhang

et al.

Leukemia, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Language: Английский

Citations

18

Design of CoQ10 crops based on evolutionary history DOI Creative Commons

Jing-Jing Xu,

Lei Yuan,

Xiaofan Zhang

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

4

Single-molecule live-cell RNA imaging with CRISPR–Csm DOI Creative Commons
Chenglong Xia, David Colognori, X. Jiang

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Abstract Understanding the diverse dynamic behaviors of individual RNA molecules in single cells requires visualizing them at high resolution real time. However, single-molecule live-cell imaging unmodified endogenous has not yet been achieved a generalizable manner. Here, we present fluorescence situ hybridization (smLiveFISH), robust approach that combines programmable RNA-guided, RNA-targeting CRISPR–Csm complex with multiplexed guide RNAs for direct and efficient visualization range cell types, including primary cells. Using smLiveFISH, track native NOTCH2 MAP1B transcripts living identify two distinct localization mechanisms cotranslational translocation mRNA endoplasmic reticulum directional transport toward periphery. This method potential to unlock principles governing spatiotemporal organization health disease.

Language: Английский

Citations

4

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

Citations

4