A Semiconducting Polymer NanoCRISPR for Near-Infrared Photoactivatable Gene Editing and Cancer Gene Therapy DOI
Yue Liu, Fei Li, Yan Lyu

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Clustered regularly interspaced short palindromic repeat (CRISPR) gene editing has poor efficacy and off-target side effect concerns. We herein report a semiconducting polymer (SP)-based nanoCRISPR system to improve CRISPR delivery allow for near-infrared (NIR) photoactivatable cancer therapy. An amphiphilic SP acts as photothermal converter, its backbone is grafted with single-stranded deoxyribonucleic acid (DNA), which enables hybridization single guide ribonucleic (sgRNA) via complementary base pairing form sgRNA/SP-DNA. This sgRNA/SP-DNA nanosystem (nanoCRISPR) can effectively deliver sgRNA into cells generate heat under NIR laser irradiation the effect. The localized triggers dissociation of DNA control release sgRNA, thereby achieving precise regulation activity. technology able precisely regulate expression green fluorescent protein (GFP) polo-like kinase 1 (PLK1) precision

Language: Английский

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials DOI Creative Commons
Roy Weinstain, Tomáš Slanina, Dnyaneshwar Kand

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(24), P. 13135 - 13272

Published: Oct. 30, 2020

Photoactivatable (alternatively, photoremovable, photoreleasable, or photocleavable) protecting groups (PPGs), also known as caged photocaged compounds, are used to enable non-invasive spatiotemporal photochemical control over the release of species interest. Recent years have seen development PPGs activatable by biologically and chemically benign visible near-infrared (NIR) light. These long-wavelength-absorbing moieties expand applicability this powerful method its accessibility non-specialist users. This review comprehensively covers organic transition metal-containing photoactivatable compounds (complexes) that absorb in visible- NIR-range various leaving gasotransmitters (carbon monoxide, nitric oxide, hydrogen sulfide). The text NIR-light-induced photosensitized using molecular sensitizers, quantum dots, upconversion second-harmonic nanoparticles, well via photodynamic (photooxygenation singlet oxygen) photothermal effects. Release from polymers, micelles, vesicles, photoswitches, along with related emerging field photopharmacology, is discussed at end review.

Language: Английский

Citations

447
Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing DOI Creative Commons
Song Zhang, Jiangtao Shen, Dali Li

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 11(2), P. 614 - 648

Published: Oct. 28, 2020

CRISPR/Cas9 genome editing has gained rapidly increasing attentions in recent years, however, the translation of this biotechnology into therapy been hindered by efficient delivery materials target cells. Direct system as a ribonucleoprotein (RNP) complex consisting Cas9 protein and single guide RNA (sgRNA) emerged powerful widespread method for due to its advantages transient reduced off-target effects. In review, we summarized current RNP systems including physical approaches synthetic carriers. The mechanisms beneficial roles these strategies intracellular were reviewed. Examples development stimuli-responsive targeted carriers are highlighted. Finally, challenges perspectives rational design next generation promising field will be discussed.

Language: Английский

Citations

303
Photocontrolled crRNA activation enables robust CRISPR-Cas12a diagnostics DOI Creative Commons

Menglu Hu,

Zhiqiang Qiu,

Zi-Rong Bi

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(26)

Published: June 21, 2022

CRISPR diagnostics based on nucleic acid amplification faces barriers to its commercial use, such as contamination risks and insufficient sensitivity. Here, we propose a robust solution involving optochemical control of RNA (crRNA) activation in detection. Based this strategy, recombinase polymerase (RPA) CRISPR-Cas12a detection systems can be integrated into completely closed test tube. crRNA designed temporarily inactivated so that RPA is not affected by Cas12a cleavage. After the reaction completed, system activated under rapid light irradiation. This photocontrolled, fully diagnostic avoids exhibits more than two orders magnitude improvement sensitivity compared with conventional one-pot assay. photocontrolled method was applied clinical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, achieving specificity comparable those PCR. Furthermore, compact automatic device constructed.

Language: Английский

Citations

137
Light‐Start CRISPR‐Cas12a Reaction with Caged crRNA Enables Rapid and Sensitive Nucleic Acid Detection DOI

Menglu Hu,

Ruhan Liu, Zhiqiang Qiu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: April 5, 2023

Abstract The clustered regularly interspaced short palindromic repeats (CRISPR) system is a promising platform for nucleic acid detection. Regulating the CRISPR reaction would be extremely useful to improve detection efficiency and speed of diagnostic applications. Here, we have developed light‐start CRISPR‐Cas12a by employing caged RNA (crRNA). When combined with recombinase polymerase amplification, robust photocontrolled one‐pot assay achieved. simpler 50‐fold more sensitive than conventional assay. This improved also facilitates development faster method. clinical samples demonstrated that 10–20 min sufficient effective detection, which much current gold‐standard technique PCR. We expect this advance in diagnostics promote its widespread applications biomedicine, agriculture, food safety.

Language: Английский

Citations

69
Modular Weaving DNAzyme in Skeleton of DNA Nanocages for Photoactivatable Catalytic Activity Regulation DOI

Hengzhi Zhao,

Deyu Yi,

Lele Li

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: March 22, 2024

Abstract DNAzymes exhibit tremendous application potentials in the field of biosensing and gene regulation due to its unique catalytic function. However, spatiotemporally controlled DNAzyme activity remains a daunting challenge, which may cause nonspecific signal leakage or silencing systems. Here, we report photochemical approach via modular weaving active into skeleton tetrahedral DNA nanocages (TDN) for light‐triggered on‐demand liberation thus conditional control activity. We demonstrate that direct encoding TDN could improve biostability ensure delivery efficiency, comparing with conventional surface anchoring strategy. Furthermore, molecular nanostructures allows remote DNAzyme‐mediated high spatiotemporal precision light. In addition, is applicable editing functions other functional nucleic acids.

Language: Английский

Citations

15
Optogenetic control of RNA function and metabolism using engineered light-switchable RNA-binding proteins DOI

Renmei Liu,

Jing Yang, Jing Yao

et al.

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(5), P. 779 - 786

Published: Jan. 3, 2022

Language: Английский

Citations

57
Orthogonal Chemical Activation of Enzyme-Inducible CRISPR/Cas9 for Cell-Selective Genome Editing DOI

Weiqi Cai,

Ji Liu,

Xianghan Chen

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(48), P. 22272 - 22280

Published: Nov. 11, 2022

The precision and therapeutic potential of CRISPR/Cas9 genome editing are greatly challenged by the less control over Cas9-mediated DNA cleavage. Herein, we introduce a conditional cell-selective system controlled disease-associated enzymes, termed enzyme-inducible CRISPR (eiCRISPR). eiCRISPR comprises Cas9 protein, self-blocked inactive single-guide RNA (bsgRNA), chemically caged deoxyribozyme (DNAzyme) that activates bsgRNA in controllable manner. We design chemical modifications DNAzyme to suppress its ability cleave blocking region bsgRNA, while decaging triggered tumor cell-overexpressed enzyme, for instance, NAD(P)H:quinone oxidoreductase (NQO1), restores activity switches on selectively cancer cells. Moreover, using biodegradable lipid nanoparticle deliver tumor-bearing xenograft, show vivo activation enables human papillomavirus 18 E6 therapy. strategy postsynthetic site-specific modification is compatible with endogenous chemistries regulating targeted gene

Language: Английский

Citations

42
An inducible CRISPR activation tool for accelerating plant regeneration DOI Creative Commons
Cuimei Zhang, Yajun Tang, Shanjie Tang

et al.

Plant Communications, Journal Year: 2024, Volume and Issue: 5(5), P. 100823 - 100823

Published: Jan. 18, 2024

The inducible CRISPR-activation (CRISPR-a) system offers unparalleled precision and versatility for regulating endogenous genes, making it highly sought after in plant research. In this study, we developed a chemically CRISPR-a tool called ER-Tag by combining the XVE with SunTag system. We systematically compared different induction strategies achieved high efficiency target gene activation. demonstrated that guide RNAs could be multiplexed pooled large-scale screening of effective morphogenic genes pairs involved regeneration. Further experiments showed induced activation these accelerated regeneration improved both eudicot monocot plants, including alfalfa, woodland strawberry sheepgrass. Our study expanded CRISPR toolset plants provided powerful new strategy studying functions when constitutive expression is not feasible or ideal.

Language: Английский

Citations

11
Recent advances in chemical modifications of guide RNA, mRNA and donor template for CRISPR-mediated genome editing DOI
Qiubing Chen, Ying Zhang, Hao Yin

et al.

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 168, P. 246 - 258

Published: Oct. 27, 2020

Language: Английский

Citations

65
Triggering biological processes: methods and applications of photocaged peptides and proteins DOI

Alicia E. Mangubat-Medina,

Zachary T. Ball

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(18), P. 10403 - 10421

Published: Jan. 1, 2021

Photocaging groups provide spatiotemporal control of function. This review surveys approaches to the design and synthesis photocaged peptides proteins, provides an overview ways in which these tools have been applied answer biological questions.

Language: Английский

Citations

41