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Honorable Mention Excerpts

Jacob Zinberg

Torah Academy of Bergen County
Teaneck, NJ
Teacher: Garry Katz

 

Cystic Fibrosis (CF) is an inherited disorder resulting from two mutated copies in the gene encoding for the cystic fibrosis trans-membrane conductance regulator (CFTR) protein. Under normal circumstances, this protein acts as a channel, transporting chloride ions out of cells and ensuring a proper salt-water balance in the mucus that lines epithelial surfaces. A mutated CFTR gene, however, cannot produce a functioning version of this protein, resulting in thick, sticky mucus that blocks the pulmonary airways and leads to lethal lung infections…

…At least 26 CF gene therapy clinical trials have been conducted since, most attempting to establish proof of concept for traditional viral-vector therapy (Griesenbach et al., 2015). Much excitement has been generated over the relatively new CRISPR-Cas9 genome editing technology in treating CF, which can correct the faulty gene instead of delivering the wild-type version via a vector…

…The researchers designed a donor DNA strand homologous to the ∆F508 sequence and tail-clamp PNA molecules (due to the “tail” of DNA left behind and edited) that bind at this particular site. Nanoparticles containing both types of molecules were tested in vitro on human CF bronchial epithelial (CFBE) cells with the ∆F508 mutation...

…also established proof of concept for in vivo use of their method by correcting ∆F508 in mice. New donor DNA and PNAs were developed to account for the slight difference in the mouse CFTR gene and were administered intranasally. Correction was confirmed by measuring the nasal potential difference (NPD), a measure of voltage (Rowe et al., 2011), in the treated nasal epithelial cells. The NPD was much greater than before treatment since the addition of the CFTR gene allowed for the transfer of chloride (Cl-) ions… 

Currently, only the symptoms of CF are treatable, and progress has been slower than anticipated in developing a repair for CFTR (Hanna et al., 2016). This innovative approach, however, will likely advance the scientific community’s overall understanding of CF gene therapies and bring these treatments to patients sooner.