The role of the CRISPR‐Cas system in cancer drug development: Mechanisms of action and therapy

Chandrasekaran, Arun Pandian; Karapurkar, Janardhan Keshav; Chung, Hee Yong; Ramakrishna, Suresh

doi:10.1002/biot.202100468

Cited by 8 publications

(7 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Efficiency of Gene Correction CRISPR-Cas9 mediated genome editing has revolutionized genetic manipulation by enabling precise modifications in cells and organisms, but usually associated with undesired outcomes including complex mixtures of products, translocations, and p53 activation. [6,19,20] Base editors enable precise, single-nucleotide changes in the DNA sequence without inducing DSBs, but currently lack the ability to install transversion point mutations, precise insertions, or precise deletions. [5] Furthermore, it can inadvertently induce bystander mutations when multiple target nucleotides exist within the editing window, and limitations in PAM availability may hinder targeting certain bases.…”

Section: Discussionmentioning

confidence: 99%

Prime editing‐mediated correction of the leptin receptor in muscle cells of db/db mice

Lee,

Xu,

Geng

et al. 2024

Biotechnology Journal

View full text Add to dashboard Cite

Genetic diseases can be caused by monogenic diseases, which result from a single gene mutation in the DNA sequence. Many innovative approaches have been developed to cure monogenic genetic diseases, namely by genome editing. A specific type of genomic editing, prime editing, has the potential advantage to edit the human genome without requiring double‐strand breaks or donor DNA templates for editing. Additionally, prime editing does not require a precisely positioned protospacer adjacent motif (PAM) sequence, which offers flexible target and more precise genomic editing. Here we detail a novel construction of a prime editing extended guide RNA (pegRNA) to target mutated leptin receptors in B6.BKS(D)‐Leprdb/J mice (db/db mice). The pegRNA was then injected into the flexor digitorum brevis (FDB) muscle of db/db mice to demonstrate in vivo efficacy, which resulted in pegRNA mediated base transversion at endogenous base transversion. Genomic DNA sequencing confirmed that prime editing could correct the mutation of leptin receptor gene in db/db mice. Furthermore, prime editing treated skeletal muscle exhibited enhanced leptin receptor signals. Thus, the current study showed in vivo efficacy of prime editing to correct mutant protein and rescue the physiology associated with functional protein.

show abstract

Section: Discussionmentioning

confidence: 99%

Prime editing‐mediated correction of the leptin receptor in muscle cells of db/db mice

Lee,

Xu,

Geng

et al. 2024

Biotechnology Journal

View full text Add to dashboard Cite

show abstract

“…Moreover, targeting ligands can be easily incorporated into MSNs to achieve targeted CRISPR-Cas9 delivery to thus reduce the off-target effects that derive from gene editing in non-targeted tissues [ 64 ]. Importantly as a dual platform, multiple combinations for gene editing and drug therapy can be envisioned by using MSNs by preparing advanced nanodevices to solve possible biomedical needs in complex diseases or restoring sensitivity in drug-resistant diseases like cancer or infections [ 64 , 65 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy

et al. 2022

View full text Add to dashboard Cite

In this article, we report one of the few examples of nanoparticles capable of simultaneously delivering CRISPR-Cas9 gene-editing machinery and releasing drugs for one-shot treatments. Considering the complexity of inflammation in diseases, the synergistic effect of nanoparticles for gene-editing/drug therapy is evaluated in an in vitro inflammatory model as proof of concept. Mesoporous silica nanoparticles (MSNs), able to deliver the CRISPR/Cas9 machinery to edit gasdermin D (GSDMD), a key protein involved in inflammatory cell death, and the anti-inflammatory drug VX-765 (GSDMD45CRISPR-VX-MSNs), were prepared. Nanoparticles allow high cargo loading and CRISPR-Cas9 plasmid protection and, thus, achieve the controlled codelivery of CRISPR-Cas9 and the drug in cells. Nanoparticles exhibit GSDMD gene editing by downregulating inflammatory cell death and achieving a combined effect on decreasing the inflammatory response by the codelivery of VX-765. Taken together, our results show the potential of MSNs as a versatile platform by allowing multiple combinations for gene editing and drug therapy to prepare advanced nanodevices to meet possible biomedical needs.

show abstract

“…Another animal model was created by surgically-transplanting xenograft from a patient into immunodeficient mice. This patient-derived xenograft (PDX) cancer model may maintain the histologic heterogeneity of the patient’s tumor ( Chandrasekaran et al, 2022 ). Researchers induced immune deficiency in Sprague-Dawley rats by knockout of Rag1, Rag2, and Il2rg, and established a PDX model of squamous lung cancer using this novel rat model.…”

Section: Research Hotspots and Frontiersmentioning

confidence: 99%

Knowledge mapping and current trends of global research on CRISPR in the field of cancer

Liu

Zhang

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Background: Gene editing tools using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-related systems have revolutionized our understanding of cancer. The purpose of this study was to determine the distribution, collaboration, and direction of cancer research using CRISPR.Methods: Data from the Web of Science (WoS) Core Collection database were collected from 4,408 cancer publications related to CRISPR from 1 January 2013to 31 December 2022. The obtained data were analyzed using VOSviewer software for citation, co-citation, co-authorship, and co-occurrence analysis.Results: The number of annual publications has grown steadily over the past decade worldwide. The United States was shown, by far, to be the leading source of cancer publications, citations, and collaborations involving CRISPR than any other country, followed by China. Li Wei (Jilin University, China), and Harvard Medical School (Boston, MA, United States) were the author and institution with the most publications and active collaborations, respectively. The journal with the most contributions was Nature Communications (n = 147) and the journal with the most citations was Nature (n = 12,111). The research direction of oncogenic molecules, mechanisms, and cancer-related gene editing was indicated based on keyword analysis.Conclusion: The current study has provided a comprehensive overview of cancer research highlights and future trends of CRISPR, combined with a review of CRISPR applications in cancer to summarize and predict research directions and provide guidance to researchers.

show abstract

The role of the CRISPR‐Cas system in cancer drug development: Mechanisms of action and therapy

Cited by 8 publications

References 94 publications

Prime editing‐mediated correction of the leptin receptor in muscle cells of db/db mice

Prime editing‐mediated correction of the leptin receptor in muscle cells of db/db mice

Nanodevices for the Efficient Codelivery of CRISPR-Cas9 Editing Machinery and an Entrapped Cargo: A Proposal for Dual Anti-Inflammatory Therapy

Knowledge mapping and current trends of global research on CRISPR in the field of cancer

Contact Info

Product

Resources

About