![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/JCF-1-300x107.jpg\")
<\/em><\/i><\/p>\r\nJOURNAL OF CYSTIC FIBROSIS<\/b><\/strong><\/p>\r\n September 2025 AUTHORS<\/strong> SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n MOLECULAR DIAGNOSIS & THERAPY <\/b><\/strong><\/p>\r\n September 2025 AUTHORS<\/strong> SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n FRONTIERS IN PHARMACOLOGY <\/b><\/strong><\/p>\r\n August 2025 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n July 2025<\/p>\r\n SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n JOURNAL OF CYSTIC FIBROSIS<\/b><\/strong><\/p>\r\n May 2025 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n TRENDS IN MOLECULAR MEDICINE<\/b><\/strong><\/p>\r\n April 2025 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n STAR Protocols<\/b><\/strong><\/p>\r\n March 2025 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n SCIENCE TRANSLATIONAL MEDICINE<\/b><\/strong><\/p>\r\n January 2025 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n JOURNAL OF CYSTIC FIBROSIS January 2025<\/p>\r\n A W1282X cystic fibrosis mouse allows the study of pharmacological and gene-editing therapeutics to restore CFTR function SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE<\/b><\/strong><\/p>\r\n November 2024 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n CELL REPORTS MEDICINE<\/b><\/strong><\/p>\r\n May 2024 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n EUROPEAN RESPIRATORY JOURNAL January 2024<\/p>\r\n SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT <\/b><\/strong><\/p>\r\n January 2024 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n MOLECULAR THERAPY NUCLEIC ACIDS<\/b><\/strong><\/p>\r\n June 2023 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n TRENDS IN MOLECULAR MEDICINE <\/b><\/strong><\/p>\r\n April 2023 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n ERJ OPEN RESEARCH<\/b><\/strong><\/p>\r\n January 2023 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n THE JOURNAL OF CLINICAL INVESTIGATION<\/b><\/strong><\/p>\r\n July 2022 SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n PEDIATRIC PULMONOLOGY<\/b> May 2022<\/p>\r\n A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators<\/i><\/p>\r\n AUTHORS SUMMARY Between June 10 and July 1, 2021, Emily’s Entourage distributed a 38-question anonymous survey targeted at people with cystic fibrosis not benefitting from approved modulators via social media and email to people with CF and CF advocacy groups in and outside the United States regarding health status, impact of CF, unmet needs, and clinical research interest. There were 431 survey respondents representing people with CF on five continents. Survey results showed that people with CF who are ineligible, intolerant, or lack access to modulators have a high burden of disease impacting their physical and mental health. Although most are happy for those who are benefiting from modulators, they are eager for the opportunity to experience similar improvements for themselves, and willing to participate in clinical trials of new therapies.<\/p>\r\n READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n MOLECULAR THERAPY: NUCLEIC ACIDS<\/b> May 2022<\/p>\r\n Efficient suppression of endogenous CFTR nonsense mutations using anticodon-engineered transfer RNAs <\/i><\/p>\r\n AUTHORS SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n JOURNAL OF CYSTIC FIBROSIS March 2022<\/p>\r\n Functional Restoration of CFTR Nonsense Mutations in Intestinal Organoids<\/em><\/p>\r\n AUTHORS SUMMARY READ THE FULL PUBLICATION HERE<\/a><\/p>\r\n NATURE COMMUNICATIONS <\/b>
Intra-individual diversity of bacteriophage susceptibility in Burkholderia cultured from cystic fibrosis sputum<\/em><\/p>\r\n
<\/strong><\/em>Ortal Yerushalmy, Abby M. Korn, Guichan Yao, Carlos F. Gonzalez, Jason J. Gill, Linda M. Kalikin, Theodore Spilker, Lindsay J. Cavelry, Amy A. Mumford, Nathan R. Wallace, Saima Aslam, Ran Nir-Paz, Daria Van Tyne, John J. LiPuma<\/p>\r\n
<\/strong>Bacteriophage (phage) therapy is being explored to treat airway infections in people with cystic fibrosis (CF), but bacterial diversity during chronic infection may complicate treatment. In this study, Burkholderia<\/em> isolates from CF sputum samples showed mixed sensitivity and resistance to phages, with 75% of samples containing both phage-sensitive and phage-resistant bacteria. These findings highlight the need to account for bacterial heterogeneity when developing phage therapies for CF.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Screenshot-2025-12-12-at-1.04.39-PM-300x47.png\")
<\/em><\/i><\/p>\r\n
Personalized medicine in cystic fibrosis: Characterization of eight rare CFTR variants in intestinal organoids and cellular models<\/em><\/p>\r\n
<\/strong><\/em>Violeta Railean, Cl\u00e1udia S. Rodrigues, Ines Pankonien, Sofia S. Ramalho, Iris A. L. Silva, Tereza Dou\u0161ov\u00e1, Susana Castanhinha, Pilar Azevedo, Juliana Roda, Carlos M. Farinha, Margarida D. Amaral<\/p>\r\n
<\/strong>This study evaluated eight rare CFTR variants to determine whether currently approved CFTR modulator (CFTRm) drugs could restore their function. Using patient-derived intestinal organoids and CF bronchial epithelial cells, the researchers found that most variants were rescued by CFTRm therapy, and patients who received treatment showed improved lung function and reduced sweat chloride levels. These results demonstrate that organoid-based assays can effectively predict clinical response to CFTR modulators for people with rare CFTR mutations.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/frontiers-in-pharmacology.png-300x82.webp\")
<\/em><\/i><\/p>\r\n
CFTR ion transport deficiency primes the epithelium for partial epithelial-mesenchymal transition in cystic fibrosis
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Cl\u00e1udia S. Rodrigues, Matilde Canto, Raquel Torres, Violeta Railean, Sofia S. Ramalho, Carlos M. Farinha, Ines Pankonien, Margarida D. Amaral<\/p>\r\n
<\/strong>Cystic fibrosis (CF) is a monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a Cl\u2212<\/sup>\/HCO3<\/sub>\u2212<\/sup> ion channel located at the apical plasma membrane (PM) of epithelial cells. CFTR dysfunction disrupts epithelial barrier integrity, drives progressive airway remodelling and has been associated with epithelial-to-mesenchymal transition (EMT), a process in which cells lose epithelial properties and acquire mesenchymal characteristics. We previously demonstrated that mutant CFTR directly drives partial EMT, independently of secondary events such as bacterial infection or inflammation.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Screenshot-2025-08-18-at-12.37.52-PM.png\")
NUCLEIC ACIDS RESEARCH<\/b><\/strong><\/p>\r\n
ACE-tRNAs are a platform technology for suppressing nonsense mutations that cause cystic fibrosis
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Wooree Ko, Joseph J. Porter, Sacha Spelier, Emily G. Sorensen, Priyanka Bhatt, Jeffery T. Gabell, Isabelle van der Windt, Tyler Couch, Kevin Coote, Martin Mense, Jeffrey M. Beekman, John D. Lueck<\/p>\r\n
<\/strong>This study demonstrates that anticodon-edited tRNAs can efficiently suppress the most common cystic fibrosis\u2013causing nonsense mutations, restoring CFTR transcript abundance and channel function across multiple patient-derived models, highlighting their potential as a therapeutic platform for CF and other nonsense-associated diseases.<\/p>\r\n
\r\n<\/em><\/i><\/p>\r\n
Personalized therapy with CFTR modulators: Response of p.Ile148Asn variant
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Cl\u00e1udia S. Rodrigues, Matilde Canto, Raquel Torres, Violeta Railean, Sofia S. Ramalho, Carlos M. Farinha, Ines Pankonien, Margarida D. Amaral<\/p>\r\n
<\/strong>Understanding how different CFTR variants affect cellular function is key to predicting disease severity, guiding genetic counseling, and choosing the right therapies for people with cystic fibrosis (CF). While current CFTR modulators mainly target the common p.Phe508del variant, rare variants like p.Ile148Asn may also respond to these drugs. This study characterized the p.Ile148Asn variant, examining its processing, trafficking, and function, as well as its response to existing modulators, suggesting potential clinical benefit for affected individuals.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/4HGv4I9n_400x400-300x300.jpg\")
<\/em><\/i><\/p>\r\n
Cystic fibrosis at a glance: from disease mechanism to therapy
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Kasper Gryspeert, Laudonia L. Dipalo, Ana L. Da Silva Cunha, Mattijs Bullpen, Marjolein M. Ensinck, Marianne S. Carlon <\/p>\r\n
<\/strong>Cystic fibrosis (CF), an autosomal recessive genetic disorder, affects around 180 000 people globally, predominantly in the Caucasian population. Symptoms arise from dehydration and accumulation of thick, sticky mucus in multiple organs. Severe symptoms include chronic lung infections, bronchiectasis, and pancreatic insufficiency, which can lead to life-threatening complications. As life expectancy has increased due to improved medical care, co-morbidities such as diabetes, liver disease, and osteoporosis have arisen.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/CellPress_STARProtocols_SponsorLogo_1080x1080-300x300.jpg\")
<\/em><\/i><\/p>\r\n
Protocol for functional screening of CFTR-targeted genetic therapies in patient-derived organoids using DETECTOR deep-learning-based analysis
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Mattijis Bulcaen, Ronald B. Lui, Kasper Gyrspeert, Sam Thierry, Anabela S. Ramalho, Fran\u00e7ois Vermeulen, Xavier Casadevall I Solvas, Marianne S. Carlon<\/p>\r\n
<\/strong>Here, the research team presents a protocol for the rapid functional screening of gene editing and addition strategies in patient-derived organoids using the deep-learning-based tool DETECT<\/i>OR (detection of targeted editing of cystic fibrosis transmembrane conductance regulator [CFTR<\/i>] in organoids). They describe steps for wet-lab experiments, image acquisition, and CFTR function analysis by DETECT<\/i>OR. They also detail procedures for applying pre-trained models and training custom models on new customized datasets.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/scitm.png-300x90.webp\")
<\/em><\/i><\/p>\r\n
Undocking of an extensive ciliary network induces proteostasis and cell fate switching resulting in severe primary ciliary dyskinesia
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Steven L. Brody, Jiehong Pan, Tao Huang, Jian Xu, Jeffrey R. Koenitizer, Steven K. Brennan, Rashmi Nanjundappa, Thomas G. Saba, Nisreen Rumman, Andrew Berical, Finn J. Jawkins, Xiangli Wang, Rui Zhang, Moe R. Mahjoub, Amjad Horani, Susan K. Dutcher<\/p>\r\n
<\/strong>Primary ciliary dyskinesia (PCD) caused by CCDC39 or CCDC40 variants leads to more severe disease than other PCD mutations. Brody and colleagues showed that loss of the CCDC39\/CCDC40 heterodimer disrupts ciliary protein networks, shifts cell fate from multiciliated to mucus-producing cells, and compromises the periciliary barrier. Restoring normal CCDC39 function in affected cells improved these defects, highlighting the potential for gene therapy in PCD.<\/p>\r\n
\r\n<\/em><\/i><\/p>\r\n
<\/b><\/strong><\/p>\r\n
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Margaret Michicich, Zachary Traylor, Caitlan McCoy, Dana M. Valerio, Alma Wilson, Molly Schneider, Sakeena Davis, Amanda Barabas, Rachel J. Mann, David F. LePage, Weihong Jiang, Mitchell L. Drumm, Thomas J. Kelley, Ronald A. Conlon, Craig A. Hodges<\/p>\r\n
<\/strong>This study introduces the first W1282X-specific mouse model of cystic fibrosis under endogenous regulatory control, demonstrating similar disease manifestations to other CF mouse models but revealing substantially different responses to therapeutic agents compared to the G542X model, underscoring the need for mutation-specific strategies and advancing the case for precision medicine in treating nonsense mutation-related CF.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/american-journal-of-respiratory-and-critical-care-medicine-small-logo-300x129.jpg\"){kind=logo}
<\/em><\/i><\/p>\r\n
Airway disease modeling with gene-edited human basal cell transplantation
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Andrew C. Berical, Hirofumi Kiyokawa, Mary Lou Beerman, Daniel Wallman, Gabrielle Cherfane, Victoria Dunphy, Jiehong Pan, Andrew Tilston-Lunel, Xaralabos Varelas, Amjad Horani, Steven L. Brody, Darrell N. Kotton, Finn J. Hawkins<\/p>\r\n
<\/strong>Researchers developed clonal airway basal cells (BCs) from human induced pluripotent stem cells (iPSCs) and used CRISPR-Cas9 to edit genes commonly mutated in primary ciliary dyskinesia (PCD). These edited BCs retained stem cell properties, formed differentiated mucociliary epithelium, and displayed expected ciliary defects, confirming successful gene knockout. This platform enables rapid in vitro and in vivo modeling of genotype-phenotype relationships and could accelerate therapeutic development for genetic lung diseases like PCD and cystic fibrosis.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/cell-reports-medicine-300x98.jpg\")
<\/em><\/i><\/p>\r\n
Prime editing functionally corrects cystic fibrosis causing CFTR mutations in human organoids and airway epithelial cells
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Mattijs Bulcaen, Phe\u00b4line Kortleven, Ronald B. Liu, Isabelle Sermet-Gaudelus, Anna Cereseto, Marianne S. Carlon<\/p>\r\n
<\/strong>Prime editing is a recent, CRISPR-derived genome editing technology capable of introducing precise nucleotide substitutions, insertions, and deletions. Here, we present prime editing approaches to correct L227R- and N1303K-CFTR, two mutations that cause cystic fibrosis and are not eligible for current market-approved modulator therapies. We show that, upon DNA correction of the CFTR gene, the complex glycosylation, localization, and, most importantly, function of the CFTR protein are restored in HEK293T and 16HBE cell lines. These findings were subsequently validated in patient-derived rectal organoids and human nasal epithelial cells. Through analysis of predicted and experimentally identified candidate off-target sites in primary stem cells, we confirm previous reports on the high prime editor (PE) specificity and its potential for a curative CF gene editing therapy. To facilitate future screening of genetic strategies in a translational CF model, a machine learning algorithm was developed for dynamic quantification of CFTR function in organoids (DETECTOR: \u2018\u2018detection of targeted editing of CFTR in organoids\u2019\u2019).<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/ERJ-Masthead_1-e1728997340795.png\")
<\/em><\/i><\/p>\r\n
<\/b><\/strong><\/p>\r\n
Organoid-guided synergistic treatment of minimal function CFTR mutations with CFTR modulators, roflumilast and simvastatin: a personalized approach
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Sacha Spelier, Karin de Winter-de Groot, Natascha Keijzer-Nieuwenhuijze, Yves Liem, Kors van der Ent, Jeffrey Beekman, Kieke S Kamphuis<\/p>\r\n
<\/strong>This study describes how preclinical research has guided a successful personalized clinical treatment regimen in a person with minimal function CFTR, upon a synergistic treatment regimen consisting of CFTR modulators, simvastatin and roflumilast.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Screenshot-2025-12-12-at-11.57.50-AM-300x90.png\")
<\/em><\/i><\/p>\r\n
Genetic surgery for a cystic fibrosis-causing splicing mutation
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Mattijs Bulcaen, Marianne S. Carlon <\/p>\r\n
<\/strong>Cystic fibrosis (CF) is caused by mutations in the CFTR gene, and while therapies exist for common mutations like F508del, people with rare splicing, nonsense, or indel mutations\u2014the \u201clast 10%\u201d\u2014still lack effective treatments. Building on previous work, researchers used CRISPR-Cas9 delivered via lipid nanoparticles to correct the c.3718-2477C>T mutation, restoring normal CFTR mRNA and significantly improving CFTR function in airway cells, with no off-target effects detected in initial analyses. While further safety testing is needed for clinical use, this approach represents a promising gene-editing strategy for CF patients who remain ineligible for current modulator therapies.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Screenshot-2025-12-12-at-11.49.41-AM-300x83.png\")
<\/em><\/i><\/p>\r\n
Nanoblades allow high-level genome editing in murine and human organoids
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Victor Tiroille, Adrien Krug, Emma Bokobza, Marianne S. Carlon, Fr\u00e9d\u00e9ric Bost, Els Verhoeyen <\/p>\r\n
<\/strong>CRISPR-Cas9 gene editing in organoids has been limited by inefficient delivery methods and toxicity. This study used \u201cnanoblade\u201d (NB) technology to achieve high-efficiency gene knockouts\u2014up to 75% in murine and 20\u201350% in human organoids\u2014without harming the cells. NBs enable rapid, stable genome editing in organoids in just four weeks with minimal off-target effects.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Screenshot-2025-12-12-at-11.31.33-AM-300x52.png\")
<\/em><\/i><\/p>\r\n
Readthrough compounds for nonsense mutations: riding the translational gap
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Sacha Speller, Eveline P.M. van Doom, Cornelis K. van der Ent, Jeffrey M. Beekman, Martijn A.J. Koppens<\/p>\r\n
<\/strong>About 10% of disease-causing mutations are nonsense mutations, which lead to severe genetic disorders with no current treatments. One common approach is to promote ribosomal readthrough of premature stop codons to restore full-length protein production. While many compounds have shown promise in preclinical studies, clinical trials have been largely unsuccessful, and this review examines the research and factors contributing to this translational gap.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Screenshot-2025-12-12-at-11.38.47-AM-300x98.png\")
<\/em><\/i><\/p>\r\n
High-throughput functional assay in cystic fibrosis patient-derived organoids allows drug repurposing
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Sacha Speller, Eyleen de Poel, Georgia N. Ithakisiou, Sylvia W.F. Suen, Marne C. Hagemeijer, Danya Muilwijk, Annelotte M. Vonk, Jesse E. Brunsveld, Evelien Kruisselbrink, Cornelis K. van der Ent, Jeffrey M. Beekman.<\/p>\r\n
<\/strong>Cystic fibrosis (CF) therapies have improved for common mutations like F508del, but people with rare CFTR mutations, such as the nonsense mutations G542X and W1282X, still lack effective treatments. In this study, researchers miniaturized a forskolin-induced swelling (FIS) assay in intestinal organoids to screen 1,400 FDA-approved compounds for their ability to increase CFTR function in W1282X\/W1282X organoids. They found that several statins, when combined with CFTR modulators, specifically and dose-dependently improved CFTR function, highlighting a potential new therapeutic approach for this mutation.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/jci-300x80.jpg\")
<\/em><\/i><\/p>\r\n
Small-molecule eRF3a degraders rescue CFTR nonsense mutations by promoting premature termination codon readthrough
<\/em>AUTHORS<\/strong>
<\/strong><\/em>Rhianna E. Lee, Catherine A. Lewis, Lihua He, Emily C. Bulkin-Sullivan, Samuel C. Gallant, Teresa M. Mascenik, Hong Dang, Deborah M. Cholon, Martina Gentzsch, Lisa C. Morton, John T. Minges, Jonathan W. Theile, Neil A. Castle, Michael R. Knowles, Adam J. Kimple, Scott H. Randell <\/p>\r\n
<\/strong>Most people with cystic fibrosis (CF) can now benefit from CFTR modulators, but those with premature termination codons (PTCs) or rare CFTR variants have limited options. To study these rare variants, researchers developed Bmi-1\/hTERT airway cell lines that replicated primary cell morphology and function, including responses to CFTR modulators. Using these lines, they showed that eRF3a-targeting compounds could partially restore CFTR function in PTC variants and revealed a potential new approach to treat these hard-to-treat CF mutations.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/Pediatric-Pulmonology-300x38.webp\")
<\/strong><\/p>\r\n
<\/strong>Emily Kramer-Golinkoff MBE, Amanda Camacho MSW, Liza Kramer MSW, Jennifer L. Taylor-Cousar MD, MSCS, ATSF<\/p>\r\n
<\/strong><\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/MOLECULAR-THERAPY-NUCLEIC-ACIDS-300x113.png\")
<\/strong><\/p>\r\n
<\/strong>Wooree Ko, Joseph J. Porter, Matthew T. Sipple, Katherine M. Edwards, John D. Lueck<\/p>\r\n
<\/strong>Suppressor tRNAs have long been identified as a possible therapeutic for nonsense-associated diseases; however, their ability to inhibit nonsense-mediated mRNA decay (NMD) and support significant protein translation from endogenous transcripts has not been determined in mammalian cells. Here, we investigated the ability of anticodon edited (ACE)-tRNAs to suppress cystic fibrosis (CF) causing PTCs in the cystic fibrosis transmembrane regulator (CFTR) gene in gene-edited immortalized human bronchial epithelial (16HBEge) cells. This study establishes the ACE-tRNA approach as a potential standalone therapeutic for nonsense-associated diseases due to its ability to rescue both mRNA and full-length protein expression from PTC-containing endogenous genes.<\/p>\r\n
\r\n![\"\"](\"https:\/\/www.emilysentourage.org\/wp-content\/uploads\/JCF.jpg\")
<\/strong><\/p>\r\n
<\/strong>E. de Poel, S. Spelier, S.W.F. Suen, E. Kruisselbrink, S.Y. Graeber, M.A. Mall, E.J.M. Weersink, M.M. van der Eerden, G. Koppelman, C.K. van der Ent, J.M. Beekman<\/p>\r\n
<\/strong>Pharmacotherapies for people with cystic fibrosis (pwCF) carrying premature termination codons (PTCs) in the CFTR gene were under development. Clinical studies had focused on compounds inducing translational readthrough (RT), and recent work showed that combining multiple modes of action could restore PTC function. Here, the research team assessed CFTR function in PTC-containing intestinal organoids using compounds targeting RT, nonsense-mediated mRNA decay (NMD), and CFTR protein modulation.<\/p>\r\n
\r\n