Developing a CRISPR/Cas9 Plasmid Vector Containing Specific Single Guide RNAs Targeting SMO in the Sonic Hedgehog Signaling Pathway for SHH-Driven Cancers.

Background & Objective: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system is considered an efficient tool for genomic engineering in the field of cancer/gene therapy. Developing a plasmid vector to target the signaling pathway of sonic hedgehog (SHH),...

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Publicado en:Journal of Advances in Medical & Biomedical Research Vol. 34; no. 1; pp. 23 - 31
Autores principales: Ghorbanlou, Mehrdad, Salimi-Jeda, Ali, Razavi, Mohamad Reza, Shabani, Ronak, Moradi, Fatemeh, Marzban, Hassan, Mehdizadeh, Mehdi
Formato: pictorial research tables/charts Journal Article
Publicado: Zanjan University of Medical Sciences & Health Services Jan/Feb2026
Acceso en línea:Ver este registro en EBSCOhost
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        atl: Developing a CRISPR/Cas9 Plasmid Vector Containing Specific Single Guide RNAs Targeting SMO in the Sonic Hedgehog Signaling Pathway for SHH-Driven Cancers.
      aug:
        au:
          Ghorbanlou, Mehrdad
          Salimi-Jeda, Ali
          Razavi, Mohamad Reza
          Shabani, Ronak
          Moradi, Fatemeh
          Marzban, Hassan
          Mehdizadeh, Mehdi
        affil: Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
      sug:
        subj:
          Gene Editing
          Oncogenes
          RNA
          Signal Transduction
          Hedgehog Signaling Proteins Antagonists and Inhibitors
          Neoplasms Drug Therapy
          Plasmids Therapeutic Use
          Genetics
          Human
          Experimental Studies
          In Vitro Studies
          In Vivo Studies
          Tumor Cells, Cultured
          Sequence Analysis
          Polymerase Chain Reaction
          Apoptosis
          Cell Viability
          Molecular Biology
          Escherichia Coli
          Glioma
      ab: Background & Objective: Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system is considered an efficient tool for genomic engineering in the field of cancer/gene therapy. Developing a plasmid vector to target the signaling pathway of sonic hedgehog (SHH), a key driver of malignancies such as medulloblastoma and basal cell carcinoma, is the aim of this study. Materials & Methods: CRISPOR online platform was used to select three specific and efficient gRNAs (guide RNAs) to design and then synthesize a gRNA cassette in a plasmid vector to target SHH pathway. Following digestion of pCas-guide-EF1aGFP, the Cas9 expressing vector, by BsrGI and BamHI restriction enzymes and ligation with T4 ligase, the gRNA cassette was cloned. After that, competent DH5α E. coli bacteria were used to amplificate the vector. Finally, after plasmid extraction, presence of the gRNA cassette was confirmed through DNA sequencing and polymerase chain reaction (PCR). Results: To target SMO gene, as an upstream target of SHH pathway, three targetprone exons (2nd, 4th, and 6th) were used to synthesize efficient and specific gRNAs. The process of cloning and developing the interested vector was confirmed by sequencing and PCR. Conclusion: Although this study lacks in vitro/in vivo validation of the candidate gRNAs within the plasmid vector, developing efficient, and specific CRISPR/Cas9 vectors may possibly be a promising approach in the field of cancer treatment through targeting neoplastic pathways at the level of positive regulators which may possibly lead to a better perception of different molecular pathways leading to cancer, and developing precise chemotherapeutic agents.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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