Near-infrared upconversion–activated CRISPR-Cas9 system: A remote-controlled gene editing platform

Pan, Yongchun; Yang, Jingjing; Luan, Xiaowei; Liu, Xinli; Li, Xueqing; Yang, Jian; Huang, Ting; Sun, Lu; Wang, Yuzhen; Lin, Youhui; Song, Yujun

doi:10.1126/sciadv.aav7199

Cited by 222 publications

(134 citation statements)

References 45 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…For example, after administration nanocarriers can be activated by an external stimuli, such as light. [161][162][163] Ren et al developed nanocarriers that sequentially release miRNA in response to pH and doxorubicin in response to near-infrared-radiation (NIR). [164] They loaded doxorubicin inside a hollow gold nanoparticle, and then attached polyamidoamine (PAMAM) around the gold nanoparticle.…”

Section: Using Systems Biology To Optimize Payload Selection and Sequmentioning

confidence: 99%

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

et al. 2020

View full text Add to dashboard Cite

Many clinical trials for cancer precision medicine have yielded unsatisfactory results due to challenges such as drug resistance and low efficacy. Drug resistance is often caused by the complex compensatory regulation within the biomolecular network in a cancer cell. Recently, systems biological studies have modeled and simulated such complex networks to unravel the hidden mechanisms of drug resistance and identify promising new drug targets or combinatorial or sequential treatments for overcoming resistance to anticancer drugs. However, many of the identified targets or treatments present major difficulties for drug development and clinical application. Nanocarriers represent a path forward for developing therapies with these “undruggable” targets or those that require precise combinatorial or sequential application, for which conventional drug delivery mechanisms are unsuitable. Conversely, a challenge in nanomedicine has been low efficacy due to heterogeneity of cancers in patients. This problem can also be resolved through systems biological approaches by identifying personalized targets for individual patients or promoting the drug responses. Therefore, integration of systems biology and nanomaterial engineering will enable the clinical application of cancer precision medicine to overcome both drug resistance of conventional treatments and low efficacy of nanomedicine due to patient heterogeneity.

show abstract

Section: Using Systems Biology To Optimize Payload Selection and Sequmentioning

confidence: 99%

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Pan et al applied this approach in CRISPR gene editing for cancer therapeutics. [193] They coated the UCN surface with ONB-caged Cas9-sgRNA, a single guide RNA that targets a tumor gene (polo-like kinase-1). NIR irradiation led to desired gene editing as verified by inhibition of tumor growth in vivo.…”

Section: Nucleotidesmentioning

confidence: 99%

“…NIR irradiation led to desired gene editing as verified by inhibition of tumor growth in vivo. [193] Another example for gene release involved UCN loaded with an ONB-caged morpholino oligonucleotide on the surface. [194] This system enabled NIR-triggered gene escape in endosomes by which gene knockdown occurred more effectively in a melanoma model.…”

Section: Nucleotidesmentioning

confidence: 99%

“…As summarized in Table 1, its applications are validated in a wide range of therapeutic molecules from antitumor agents [11,13,103,202] (DOX, [23,203] 5-FU, [140] MTX, [24,138] paclitaxel, [126,177] camptothecin [182] ), antibacterial agents, [172] gas molecules (NO, [195,197] CO, [199] H 2 S [201] ) to nucleotides. [193] 5. Therapeutic Release via Photolytic Disassembly…”

Section: Gas Molecules Of Biological Significancementioning

confidence: 99%

See 1 more Smart Citation

Photoactivation Strategies for Therapeutic Release in Nanodelivery Systems

Choi

2020

Advanced Therapeutics

View full text Add to dashboard Cite

Control of therapeutic release constitutes one of most critical aspects considered in the design of nanoscale delivery systems. There are a variety of cellular factors and external stimuli employed for release control. Of these, use of light offers various photoactivation mechanisms that enable to effectively engage in therapeutic release. It also allows a higher degree of spatial and temporal control. Over recent decades, the application of photoactivation strategies has seen remarkable growth and made a significant impact on rapid advances in the field of drug delivery. This Review aims to summarize the fundamental concepts and practical applications demonstrated recently in numerous therapeutic areas from cancers to infectious diseases. Its scope is defined by a focus on those photoactivation strategies that occur via either linker cleavage, nanocontainer gating, or disassembly. Each of these is discussed with specific examples and underlying mechanisms that comprise linker photolysis, photoisomerization, photothermal heating, or photodynamic reactions with reactive oxygen species. In summary, this Review provides an inclusive summary of new developments and insights obtained from recent progress in photoactivation strategies and their applications in therapeutic nanodelivery.

show abstract

“…To address these issues, far-red light-mediated CRISPR-dCas9 device, which is built based on the bacterial photoactivatable cyclic diguanylate monophosphate (c-di-GMP) synthase BphS and the c-di-GMP-responsive hybrid transactivator, has been recently developed for the targeted epigenetic modulation both in vitro and in vivo 34 . Most recently, near-infrared upconversion-activated CRISPR-Cas9 nanoparticle system have been proposed for the optical control of therapeutic gene editing towards cancer treatment 35 . While above two studies revealed the infrared light is critical for the regulation of genome editing and epigenome editing in vivo, the precise CRISPR/Cas9 genome editing in a programmable, reversible manner has not been demonstrated yet, not to mention those for in vivo applications.…”

Section: Introductionmentioning

confidence: 99%

Optogenetic Control of Programmable Genome Editing by Photoactivatable CRISPR/Cas9 Nanosystem in the Second Near-Infrared Window

Chen

Xin

et al. 2019

Preprint

View full text Add to dashboard Cite

53We herein report the first optogenetically activatable CRISPR/Cas9 nanosystem for 54 programmable genome editing in the second near-infrared (NIR-II) optical window. The 55 nanosystem is composed of a cationic polymer-coated gold nanorod (APC) and Cas9 56 plasmid driven by a heat-inducible promoter. APC not only serves as a carrier for 57 intracellular plasmid delivery, but also can harvest external NIR-II photonic energy and 58 convert into local heat to induce the gene expression of Cas9 endonuclease. Due to high 59 transfection activity, APC shows strong ability to induce significant level of disruption in 60 different genome loci upon optogenetic activation. Moreover, the precise control of 61 genome editing activity can be simply programmed by finely tuning exposure time and 62 irradiation times in vitro and in vivo, and also enables editing at multiple time points, thus 63 proving the sensitivity and reversibility of such an editing modality. The NIR-II optical 64 feature of APC enables therapeutic genome editing at the deep tissue of the tumor-65 bearing mice, by which tumor growth could be effectively inhibited as a proof-of-concept 66 therapeutic example. Importantly, this modality of optogenetic genome editing can 67 significantly minimize the off-target effect of CRISPR/Cas9 in the most potential off-target 68 sites. The optogenetically activatable CRISPR/Cas9 nanosystem we have developed 69 offers a useful tool to expand the current applications of CRISPR/Cas9, and also defines 70 a programmable genome editing strategy towards unprecedented precision and 71 spatiotemporal specificity. 72 Introduction 73The RNA-guided clustered, regularly interspaced, short palindromic repeats (CRISPR)-74 associated nuclease protein 9 (Cas9) is originally an adaptive immune defense system, 75 by which many bacteria exploit to protect themselves from invading genetic elements 1 . It 76 has been recently harnessed as an efficient tool for genome editing in both single cells 77 and the whole organism for a wide range of biomedical applications in biology, genetics, 78 and medicine, etc 2,3 . In principle, the CRISPR/Cas9 is composed a single-guide RNA 79 (sgRNA) for the identification of DNA targets and a Cas9 endonuclease that can bind 80 and process the recognized DNA targets 4 . CRISPR/Cas9-based genome editing 81 technology offers a powerful and reliable strategy for the targeted modifications of the 82 genome, enabling the precise perturbation of virtually any genomic sequence in living 83 cells 2-6 . Due to its genome-wide specificity and multiplexing capability, Cas9 and its 84 variants have shown great potentials in the generation of loss-of-function animals 7,8 , the 85 correction of genetic disorders 9,10 , functional genome screening [11][12][13][14][15] , and the treatment of 86 infectious diseases 16,17 . Despite of these excitements, the lack of temporal and spatial 87 precision during editing process has severely constrained the current CRISPR/Cas9 88 systems from complicated and diverse genome-editing s...

show abstract

Near-infrared upconversion–activated CRISPR-Cas9 system: A remote-controlled gene editing platform

Cited by 222 publications

References 45 publications

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

Realizing Cancer Precision Medicine by Integrating Systems Biology and Nanomaterial Engineering

Photoactivation Strategies for Therapeutic Release in Nanodelivery Systems

Optogenetic Control of Programmable Genome Editing by Photoactivatable CRISPR/Cas9 Nanosystem in the Second Near-Infrared Window

Contact Info

Product

Resources

About