Michael Sebastian Daniel Kormann

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### **Abstract**

The cystic fibrosis transmembrane conductance regulator (CFTR) gene was cloned over two decades ago and a vast number of pre-clinical and clinical studies have been performed since that time. Despite this progress, a true "cure" for the disease has not been achieved, partly because the lung is a major barrier for intruders, making it exceedingly difficult for new pharmaceutical formulations to penetrate target cells. Safety-engineered viral vectors, such as adeno-associated viral vectors (AAVs) or integrase-defective lentiviruses, have been used with moderate success in temporarily supplementing the expression of critical proteins. However, stability and safety concerns often dampen the effects of these approaches. With emerging technologies, such as modified messenger (mRNA) and new genome editing strategies, scientists are now exploring the possibility of not only supplementing defective proteins, but instead, correcting the genetic defects at their source. This chapter will highlight the theoretical possibilities and primary data in pre-clinical models supporting the efforts toward *in vivo* gene correction of cystic fibrosis (CF).

**Keywords:** Cystic fibrosis (CF), gene correction, messenger RNA (mRNA), zinc fin‐ ger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), clus‐ tered regularly interspaced short palindromic repeats (CRISPR), CRISPR/Cas9, dimeric CRISPR RNA-guided *Fok*I
