Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice DOI Creative Commons
Pengpeng Liu, Shun‐Qing Liang, Chunwei Zheng

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 9, 2021

Abstract Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor as a template. PEs facilitate nucleotide substitutions local insertions deletions within the based on template sequence encoded prime editing guide RNA (pegRNA). However, efficacy of in adult mice has not been established. Here we report an NLS-optimized SpCas9-based editor that improves efficiency both fluorescent reporter cells and at endogenous loci cultured cell lines. Using this system, could also seed tumor formation through somatic mouse. Finally, successfully utilize dual adeno-associated virus (AAVs) for delivery split-intein demonstrate system enables correction pathogenic mutation mouse liver. Our findings further establish broad potential technology directed installation modifications vivo, with important implications disease modeling correction.

Language: Английский

Evolutionary classification of CRISPR–Cas systems: a burst of class 2 and derived variants DOI
Kira S. Makarova, Yuri I. Wolf, Jaime Iranzo

et al.

Nature Reviews Microbiology, Journal Year: 2019, Volume and Issue: 18(2), P. 67 - 83

Published: Dec. 19, 2019

Language: Английский

Citations

1968
Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors DOI
Andrew V. Anzalone, Luke W. Koblan, David R. Liu

et al.

Nature Biotechnology, Journal Year: 2020, Volume and Issue: 38(7), P. 824 - 844

Published: June 22, 2020

Language: Английский

Citations

1799
Human organoids: model systems for human biology and medicine DOI Open Access
Jihoon Kim, Bon‐Kyoung Koo, Juergen A. Knoblich

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(10), P. 571 - 584

Published: July 7, 2020

Language: Английский

Citations

1601
The promise and challenge of therapeutic genome editing DOI
Jennifer A. Doudna

Nature, Journal Year: 2020, Volume and Issue: 578(7794), P. 229 - 236

Published: Feb. 12, 2020

Language: Английский

Citations

905
RNA-based therapeutics: an overview and prospectus DOI Creative Commons
Yiran Zhu, Liyuan Zhu, Xian Wang

et al.

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(7)

Published: July 23, 2022

Abstract The growing understanding of RNA functions and their crucial roles in diseases promotes the application various RNAs to selectively function on hitherto “undruggable” proteins, transcripts genes, thus potentially broadening therapeutic targets. Several RNA-based medications have been approved for clinical use, while others are still under investigation or preclinical trials. Various techniques explored promote intracellular trafficking metabolic stability, despite significant challenges developing therapeutics. In this review, mechanisms action, challenges, solutions, therapeutics comprehensively summarized.

Language: Английский

Citations

374
Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations DOI Open Access
Dragan Primorac, Vilim Molnar,

Eduard Rod

et al.

Genes, Journal Year: 2020, Volume and Issue: 11(8), P. 854 - 854

Published: July 26, 2020

Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It estimated that prevalence of knee (OA) among adults 60 years age or older approximately 10% in men and 13% women, making OA one leading causes disability elderly population. Today, we know not a disease characterized by loss cartilage due to mechanical loading only, but condition affects all tissues joint, causing detectable changes tissue architecture, its metabolism function. All these are mediated complex yet fully researched interplay proinflammatory anti-inflammatory cytokines, chemokines, growth factors adipokines, which can be measured serum, synovium histological samples, potentially serving as biomarkers stage progression. Another key aspect progression epigenome regulates genetic expression through DNA methylation, histone modifications, mRNA interference. A lot work has been put into developing non-surgical treatment options slow down natural course postpone, maybe even replace extensive surgeries such total arthroplasty. At moment, biological treatments platelet-rich plasma, bone marrow mesenchymal stem cells autologous microfragmented adipose containing stromal vascular fraction ordinarily used. Furthermore, latter two mentioned cell-based seem only methods so far increase quality patients. Yet, future, gene therapy could become option orthopedic In following review, summarized latest important research basic sciences, pathogenesis, non-operative treatment.

Language: Английский

Citations

369
CRISPR technologies for precise epigenome editing DOI
Muneaki Nakamura, Yuchen Gao, Antonia A. Dominguez

et al.

Nature Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 11 - 22

Published: Jan. 1, 2021

Language: Английский

Citations

353
Engineering microrobots for targeted cancer therapies from a medical perspective DOI Creative Commons
Christine K. Schmidt, Mariana Medina‐Sánchez, Richard J. Edmondson

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 5, 2020

Abstract Systemic chemotherapy remains the backbone of many cancer treatments. Due to its untargeted nature and severe side effects it can cause, numerous nanomedicine approaches have been developed overcome these issues. However, targeted delivery therapeutics challenging. Engineering microrobots is increasingly receiving attention in this regard. Their functionalities, particularly their motility, allow penetrate tissues reach cancers more efficiently. Here, we highlight how different microrobots, ranging from tailor-made motile bacteria tiny bubble-propelled microengines hybrid spermbots, be engineered integrate sophisticated features optimised for precision-targeting a wide range cancers. Towards this, importance integrating clinicians, public patients early on development novel technologies.

Language: Английский

Citations

340
Prime editing for precise and highly versatile genome manipulation DOI
Peter J. Chen, David R. Liu

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(3), P. 161 - 177

Published: Nov. 7, 2022

Language: Английский

Citations

315
CRISPR-Cas12a-Based Nucleic Acid Amplification-Free DNA Biosensor via Au Nanoparticle-Assisted Metal-Enhanced Fluorescence and Colorimetric Analysis DOI
Jin‐Ha Choi, Joungpyo Lim, Minkyu Shin

et al.

Nano Letters, Journal Year: 2020, Volume and Issue: 21(1), P. 693 - 699

Published: Dec. 21, 2020

Cell-free DNA (cfDNA) has attracted significant attention due to its high potential diagnose diseases, such as cancer. Still, detection by amplification method limitations because of false-positive signals and difficulty in designing target-specific primers. CRISPR-Cas-based fluorescent biosensors have been developed but also need the step for detection. In this study, first time CRISPR-Cas12a based nucleic acid amplification-free biosensor was detect cfDNA a metal-enhanced fluorescence (MEF) using DNA-functionalized Au nanoparticle (AuNP). Upon activating complex target subsequent single-strand (ssDNA) degradation between AuNP fluorophore, MEF occurred with color changes from purple red-purple. Using system, breast cancer gene-1 (BRCA-1) can be detected very sensitivity 30 min. This rapid highly selective sensor applied measure other biomarkers viral field-deployable point-of-care testing (POCT) platform.

Language: Английский

Citations

309