CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders

Abstract

Respiratory disorders are among the conditions that affect the respiratory system. The healthcare sector faces challenges due to the emergence of drug resistance to prescribed medications for these illnesses. However, there is a technology called CRISPR/Cas9, which uses RNA to guide DNA targeting. This technology has revolutionized our ability to manipulate and visualize the genome, leading to advancements in research and treatment development. It can effectively reverse epigenetic alterations that contribute to drug resistance. Some studies focused on health have shown that targeting genes using CRISPR/Cas9 can be challenging when it comes to reducing drug resistance in patients with respiratory disorders. Nevertheless, it is important to acknowledge the limitations of this technology, such as off-target effects, immune system reactions to Cas9, and challenges associated with delivery methods. Despite these limitations, this review aims to provide knowledge about CRISPR/Cas9 genome editing tools and explore how they can help overcome resistance in patients with respiratory disorders. Additionally, this study discusses concerns related to applications of CRISPR and provides an overview of successful clinical trial studies.

Keywords: CRISPR/ Cas9; Drug resistance; Respiratory disease.

Fig. 1

The schematic diagram shows the structure and mode of action of CRISPR/Cas9 for fighting drug resistance in respiratory disorders. The CRISPR/Cas9 system, consisting of the Cas9 endonuclease and single guide RNA (sgRNA), is depicted as targeting specific genomic sequences associated with drug resistance mechanisms in respiratory cells. Upon binding to its target sequence guided by sgRNA, Cas9 induces double-stranded breaks (DSBs) in the DNA and disrupts the multi-drug resistance (MDR)-related genes, thus leading to targeted genetic modifications that counteract drug resistance. The figure is made using BioRender software

Fig. 2

Illustration of induced pluripotent stem cell-based CRISPR/Cas9 technology. A patient with cystic fibrosis (CF) can undergo autologous iPS cell therapy, which involves isolating, expanding, and reprogramming their somatic cells to become induced pluripotent stem cells. These cells are then characterized into proximal airway epithelium, the genetic abnormality is fixed using CRISPR/cas9 technology to produce normal airway epithelium, and the cells are then implanted back into the recipient. The combination of allogeneic or autologous iPS cell therapy with CRISPR/Cas9 technology is a new area in stem cell therapy, allowing permanent changes in the DNA sequence precisely and personalized treatments for a wide variety of diseases and disorders. The figure is created using BioRender software

Fig. 3

Schematic showing that CRISPR/Cas9 modulates the β-catenin-miR-421-KEAP1 pathway, which mediates tumor cell death by increasing chemosensitivity in LC. CRISPR/Cas9, comprising Cas9 protein and guide RNA (gRNA), targets specific DNA sequences, initiating the pathway with β-catenin activation and subsequent downregulation of miR-421. MiR-421 upregulates KEAP1, leading to ROS activation and enhanced antioxidant capacity. As a result, increases chemosensitivity, promoting tumor cell death in lung cancer cells. The figure is made using BioRender software

Fig. 4

The schematic diagram represents the application of the CRISPR/Cas9 system for editing drug-resistant genes and identifying potential targets in respiratory diseases drug-resistant. The figure is made using BioRender software

Fig. 5

The schematic illustration represents the CRISPR/Cas9 system’s off-targeting challenges, as well as main important strategies to overcome these challenges. The figure is made using BioRender software

Fig. 6

Schematic representation illustrating the CRISPR/Cas9 system’s targeting of an MDR-related gene and correction of IPSCs cells. The CRISPR/Cas9 system is delivered into cells via a variety of techniques, including electroporation, viral vectors, and nanoparticles. After the transcription and translation of Cas9 mRNA, the Cas9 protein is Combined with sgRNA. This complex then specifically targets genes associated with multidrug resistance (MDR). Induces a break in the DNA strand. The figure is made using BioRender software