CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential

Blenke, Erik Oude; Evers, Martijn J W; Mastrobattista, Enrico; Oost, John van der

doi:10.1016/j.jconrel.2016.08.002

Cited by 58 publications

(40 citation statements)

References 91 publications

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“…For example, (i) both technologies possess the ability to knock-down a gene at the posttranscriptional level rather than to knock it out on the genomic DNA level (23,26); (ii) in around 24 hours, both treatments can exert significant posttranscriptional suppression of gene expression, if the targeting components are present in the appropriate cellular compartments at adequate doses (29); (iii) each technology can display very high efficiency to reduce transcript levels; and (iv) both have comparable delivery efficiency during in vitro cell culture experiments, but also both would have the same limitations imposed by the delivery strategy used for successful in vivo application. In this regard, although the potential clinical application is enormous, overcoming delivery obstacles remains crucial to achieve clinical success for the CRISPR-Cas13 system or any other nucleic acid-based therapeutic strategy (30,31). In this respect, if the delivery challenges and side effects are appropriately addressed, a wide variety of common deployment methods of transiently expressed CRISPR/Cas components, such as electroporation, nucleofection, and lipofectamine-mediated transfection of nonreplicating plasmids, could be adapted to suite either ex vivo or in vivo CRISPR-based RNAtargeting approaches (32).…”

Section: Common Denominators and Big Differences Among Crispr/cas13 Amentioning

confidence: 99%

CRISPR–Cas13 Precision Transcriptome Engineering in Cancer

Granados-Riverón

Aquino‐Jarquín

2018

Cancer Research

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The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated genes (Cas) system has been rapidly harnessed to perform various genomic engineering tasks. Recently, it has been demonstrated that a novel RNA-targeting CRISPR effector protein, called Cas13, binds and cleaves RNA rather than DNA substrates analogously to the eukaryotic RNA interference system. The known Cas13a-Cas13d effectors are able to efficiently cleave complementary target single-stranded RNAs, which represent a potentially safer alternative to deoxyribonuclease Cas9, because it induces loss-of-function phenotypes without genomic loss of the targeted gene. Furthermore, through the improvement in Cas13 effector functionalities, a system called REPAIR has been developed to edit full-length transcripts containing pathogenic mutations, thus providing a promising opportunity for precise base editing. Moreover, advanced engineering of this CRISPR effector also permits nucleic acid detection, allowing the identification of mutations in cell-free tumor DNA through a platform termed Specific High Sensitivity Enzymatic Reporter Unlocking. All of these properties give us a glimpse about the potential of the CRISPR toolkit for precise transcriptome engineering, possibly leading to an expansion of CRISPR technologies for cancer therapeutics and diagnostics. Here, we examine previously unaddressed aspects of the CRISPR-based RNA-targeting approach as a feasible strategy for globally interrogating gene function in cancer in a programmable manner. .

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Section: Common Denominators and Big Differences Among Crispr/cas13 Amentioning

confidence: 99%

CRISPR–Cas13 Precision Transcriptome Engineering in Cancer

Granados-Riverón

Aquino‐Jarquín

2018

Cancer Research

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“…Furthermore, the CRISPR/Cas9 system using lentivirus and adeno‐associated virus (AAV) has a variety of applications, especially in functional genomics. Very limited CRISPR/Cas9 system in vivo delivery approaches have been reported due to low viral systemic efficiency and off‐targeting ,. Furthermore, magnetic virus by binding the phage with iron oxide nanoparticles can detect the clinical infected cancer samples with the high stability, specificity, and sensitivity compared with viruses or antigens alone .…”

Section: Discussionmentioning

confidence: 99%

Micro‐scale RNA Interference using Iron Oxide Nanoparticle‐modified Lentivirus

et al. 2017

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The US Food and Drug Administration (FDA) has approved the use of virotherapy. However, significant improvements are anticipated if effective localized infection can be achieved. Herein, we demonstrate magnetic lentivirus is guided by magnetic fields. Introduction of short hairpin RNA (shRNA) into the lentivirus genome enabled micro-scale RNA interference (RNAi) therapy. Although epidermal growth factor receptor (EGFR)-targeted therapies have successfully treated individuals with non-small cell lung cancer (NSCLC) cells, clinical therapeutic outcomes have been compromised by acquired resistance to first-generation tyrosine kinase inhibitors. We assess magnetic lentivirus with NSCLC cells using an in vitro model and achieve micro-scale RNAi through EGFR silencing. This proof-of-principle study demonstrates guided and highly localized micro-scale, RNAi virotherapy.

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“…These macromolecules are not able to spontaneously enter the cells, relying on the use of delivery vehicles such as viral vectors, nanoparticles, or physical and mechanical delivery methods like nucleofection, cell squeezing, or lipofection that utilize electric field, mechanical force, or cationic lipids for temporary disruption of the cell membrane [151]. The latter are primarily suited for therapeutic ex vivo gene editing, while viral vectors and nanoparticles are mainly used for in vivo gene therapy [152]. …”

Section: Gene Editingmentioning

confidence: 99%

Advances in the delivery of RNA therapeutics: from concept to clinical reality

2017

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The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

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CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential

Cited by 58 publications

References 91 publications

CRISPR–Cas13 Precision Transcriptome Engineering in Cancer

CRISPR–Cas13 Precision Transcriptome Engineering in Cancer

Micro‐scale RNA Interference using Iron Oxide Nanoparticle‐modified Lentivirus

Advances in the delivery of RNA therapeutics: from concept to clinical reality

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