# Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies
## 6 Conclusions and Future Direction  
Our review has explained the pathogenesis of CF and the different treatment approaches that are recommended. Despite the well-identified cause of CF, its treatment strategies have proven to be very challenging. Unfortunately, no model therapeutic strategy exists for CF treatment since the variation in the mutated gene is different from patient to patient. The conventional therapeutic approaches for CF primarily focus on improving CFTR function and its associated complications. This review has covered a wide range of therapeutic approaches for use in CF patients. Small molecule modulators demonstrate significant clinical efficacy by enhancing the pulmonary function in certain CF patients, thus improving their quality of life. However, in other CF patients, where the modulators are not applicable, a combination of different classes of medications, with different mechanisms of action, can be involved in the treatment plan. Targeting bacterial biofilms using antib biofilm peptides, and using gene-editing tools like CRISPR have shown great potential for use in CF therapy. These innovative approaches, when delivered through a nanocarrier system, have proven to be significant in the treatment of CF.  
Typically, a proper gene editing therapy for CF involves a clear understanding of the mechanism of this approach, for instance, the amount of the cells needed to correct CFTR function, the type of cells in the airway tissue that will be targeted, and their lifespan. These values need to be investigated in vivo, as the genetic and non-genetic modifiers affect the in vitro testing. Additionally, this in vivo assessment must be extended to involve other channels interacting with the CFTR, like ENaC, to evaluate the restoration of CFTR function needed for clinical benefit. The gene editing technology has improved dramatically since the use of the CRISPR/Cas system in 2013 [156; 157]. Nevertheless, more precautions are required while using this system owing to the off-target effect, wherein the CRISPR system can  
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manipulate a similar genetic sequence that occurs in another genome. Another concern that needs to be considered is the immune response to the CRISPR components, gRNA and Cas9, especially in a repeat dosing regimen, which can lead to serious complications.  
Moreover, the airway epithelial tissue consists of various types of cells. Cells with predominant gene expression are considered as preferable targets for gene therapy. A recent study has identified a new cell type within the human bronchial epithelial tissue and mouse tracheal epithelial tissue known as the pulmonary ionocyte. This cell exhibits a high expression of CFTR (60%) compared to the ciliated cells (4%) [225; 226]. However, further study is required to develop a suitable vector that can efficiently target these cells.  
Finally, personalized medicine is considered to be the future of CF therapy. Here, the treatment is customized according to each patient's genomic identity. Small molecule modulator is a kind of personalized medicine used for a specific mutation class. Additionally, the expression of transforming growth factor beta 1 (_TGF-81_) and mannose-binding lectin 2 (_MBL2_) have been identified as gene modifiers for CF and infection severity [227]. Other CF modifier genes that have been reported through genome-wide association studies (_GWAS_) are Ets homologous factor (_EHF_) and APAF1 interacting protein (_APIP_) [228].  
All authors contributed to writing and editing of the manuscript. All authors have read and agreed to the published version of the manuscript.  
This research received no external funding.  
The authors declare no conflict of interest.