Three’s company: Simultaneous trimodal genome engineering using orthologous Cas proteins DOI
Imogen Brooks, J. Jackow

Molecular Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Effective Delivery of CRISPR/dCas9-SAM for Multiplex Gene Activation Based on Mesoporous Silica Nanoparticles for Bladder Cancer Therapy DOI Creative Commons

Jinming Xu,

Jiaju Xu,

Chengfang Sun

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1

Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models DOI Creative Commons
Saif Dababneh,

Hosna Babini,

Verónica Jiménez-Sábado

et al.

Stem Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102467 - 102467

Published: March 1, 2025

Language: Английский

Citations

0

CRISPR-Cas Systems: A Functional Perspective and Innovations DOI Open Access
Carla Navarro, María P. Díaz, Pablo Durán

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3645 - 3645

Published: April 12, 2025

Adaptation is a fundamental tenet of evolutionary biology and essential for the survival all organisms, including prokaryotes. The evolution clustered regularity exemplifies this principle interspaced short palindromic repeats (CRISPR) associated proteins (Cas), an adaptive immune system that confers resistance to viral infections. By integrating segments genomes into their own, bacteria archaea develop molecular memory enables them mount rapid targeted response upon subsequent challenges. fortuitous discovery mechanism prompted many studies introduced researchers novel tools could potentially be developed from CRISPR-Cas become clinically relevant as biotechnology rapidly advances in area. Thus, deeper understanding underpinnings its possible therapeutic applications required. This review analyses action systems detail summarises developing biotechnological based on CRISPR, opening field further research.

Language: Английский

Citations

0

Epigenetic Landscapes Drive CAR-T Cell Kinetics and Fate Decisions: Bridging Persistence and Resistance DOI
Kecheng Wang,

Kaixin Ou,

Yu Zeng

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: unknown, P. 104729 - 104729

Published: April 1, 2025

Language: Английский

Citations

0

Comprehensive transcription factor perturbations recapitulate fibroblast transcriptional states DOI Creative Commons
Kaden M. Southard, Rico Chandra Ardy, Anran Tang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 3, 2024

Summary Cell atlas projects have nominated recurrent transcriptional states as drivers of biological processes and disease, but their origins, regulation, properties remain unclear. To enable complementary functional studies, we developed a scalable approach for recapitulating cell in vitro using CRISPR activation (CRISPRa) Perturb-seq. Aided by novel multiplexing method, activated 1,836 transcription factors two types. Measuring 21,958 perturbations showed that CRISPRa targets within physiological ranges, epigenetic features predicted activatable genes, the protospacer seed region drove an off-target effect. Perturbations recapitulated vivo fibroblast states, including universal inflammatory identified KLF4 KLF5 key regulators state. Inducing state suppressed disease-associated highlighting its therapeutic potential. Our findings cement tool perturbing differentiated cells indicate can be elicited via perturbation, enabling studies clinically relevant ex .

Language: Английский

Citations

2

Central control of dynamic gene circuits governs T cell rest and activation DOI Creative Commons
Maya M. Arce, Jennifer M. Umhoefer, Nadia Arang

et al.

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

Published: Dec. 11, 2024

The ability of cells to maintain distinct identities and respond transient environmental signals requires tightly controlled regulation gene networks

Language: Английский

Citations

2

Decoding gene regulation with CRISPR perturbations DOI
Stefan Oberlin, Michael T. McManus

Nature Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: May 17, 2024

Language: Английский

Citations

1

HyperCas12a enables highly-multiplexed epigenome editing screens DOI
Schuyler Melore, Marisa C. Hamilton, Timothy E. Reddy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 9, 2024

Abstract Interactions between multiple genes or cis-regulatory elements (CREs) underlie a wide range of biological processes in both health and disease. High-throughput screens using dCas9 fused to epigenome editing domains have allowed researchers assess the impact activation repression coding non-coding genomic regions on phenotype interest, but assessment genetic interactions those has been limited pairs. Here, we combine hyper-efficient version Lachnospiraceae bacterium dCas12a (dHyperLbCas12a) with RNA Polymerase II expression long CRISPR (crRNA) arrays enable efficient highly-multiplexed editing. We demonstrate that this system is compatible several domains, including P300 histone acetyltransferase domain SIN3A interacting (SID). also show platform can perform simultaneous single crRNA array via co-expression orthologues. Lastly, highly effective for high-throughput screens. use dHyperLbCas12a-KRAB ∼19,000-member barcoded library containing six crRNAs each dissect independent combinatorial contributions CREs dose-dependent control gene at glucocorticoid-responsive locus. The tools methods introduced here create new possibilities multiplexed variety systems.

Language: Английский

Citations

0

Gene circuit-based sensors DOI Creative Commons
Xinyue Guo, Min Li, Xiaolei Zuo

et al.

Fundamental Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

As an important branch of biosensors, gene circuit-based biosensors constructed based on synthetic biology concepts can sense specific substances to be measured and converted into signal outputs. Such sensors have great potential in the fields biomanufacturing process monitoring, environmental food safety, medical diagnosis, monitoring. With development technology abundance genetic components, more cell-free microbial with different response mechanisms, logic gates, loops been developed. This review integrates basic comprehensively describe design engineering circuits, overview systems (CFS), CFS. Emphasis is placed concepts, construction principles, applications cell-free-based field bioassay. We also discuss new frontiers challenges addressed.

Language: Английский

Citations

0

PreciCE: Precision engineering of cell fates via data-driven multi-gene control of transcriptional networks DOI Creative Commons
Jens P. Magnusson, Yusuf Roohani,

Daniel Stauber

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract The directed differentiation of stem cells into specific cell types is critical for regenerative medicine and cell-based applications. However, current methods fate control are inefficient, imprecise, rely on laborious trial-and-error. To address these limitations, we present a method data-driven multi-gene modulation transcriptional networks. We develop bidirectional CRISPR-based tools based dCas12a, Cas13d, dCas9 simultaneously activating repressing many genes. Due to the vast combinatorial complexity regulation, introduce machine learning-based computational algorithm that uses single-cell RNA sequencing data predict perturbation sets converting starting type desired target type. By combining technologies, establish unified workflow engineering demonstrate its efficacy in controlling early while suppressing alternative lineages through logic-based operations. This approach represents significant advancement use synthetic biology engineer identity.

Language: Английский

Citations

0