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Engineered amphiphilic peptides enable delivery of proteins and CRISPR-associated nucleases to airway epithelia.
Krishnamurthy S, Wohlford-Lenane C, Kandimalla S, Sartre G, Meyerholz DK, Théberge V, Hallée S, Duperré AM, Del'Guidice T, Lepetit-Stoffaes JP, Barbeau X, Guay D, McCray PB Jr. Krishnamurthy S, et al. Nat Commun. 2019 Oct 28;10(1):4906. doi: 10.1038/s41467-019-12922-y. Nat Commun. 2019. PMID: 31659165 Free PMC article.
Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSA(mT/mG) mice. We observe no evidence of short-term toxicity with a widespread distribution restricted to the respiratory tract. ...
Instillation of shuttle peptides combined with SpCas9 or AsCas12a RNP achieves editing of loxP sites in airway epithelia of ROSA(mT/mG) mice …
A Novel AAV-mediated Gene Delivery System Corrects CFTR Function in Pigs.
Cooney AL, Thornell IM, Singh BK, Shah VS, Stoltz DA, McCray PB Jr, Zabner J, Sinn PL. Cooney AL, et al. Am J Respir Cell Mol Biol. 2019 Dec;61(6):747-754. doi: 10.1165/rcmb.2019-0006OC. Am J Respir Cell Mol Biol. 2019. PMID: 31184507 Free PMC article.
Because of the packaging constraints of AAV, careful consideration was required to ensure that the vector would package and express its CFTR cDNA cargo. In this short-term study, PB/AAV-CFTR was aerosolized to the airways of CF pigs in the absence of the transposase. ...
Because of the packaging constraints of AAV, careful consideration was required to ensure that the vector would package and express its CFTR …
In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis.
Sun X, Yi Y, Yan Z, Rosen BH, Liang B, Winter MC, Evans TIA, Rotti PG, Yang Y, Gray JS, Park SY, Zhou W, Zhang Y, Moll SR, Woody L, Tran DM, Jiang L, Vonk AM, Beekman JM, Negulescu P, Van Goor F, Fiorino DF, Gibson-Corley KN, Engelhardt JF. Sun X, et al. Sci Transl Med. 2019 Mar 27;11(485):eaau7531. doi: 10.1126/scitranslmed.aau7531. Sci Transl Med. 2019. PMID: 30918114 Free PMC article.
In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. ...VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidi …
In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pa …
Lentiviral Vectors for the Treatment and Prevention of Cystic Fibrosis Lung Disease.
Marquez Loza LI, Yuen EC, McCray PB Jr. Marquez Loza LI, et al. Genes (Basel). 2019 Mar 14;10(3):218. doi: 10.3390/genes10030218. Genes (Basel). 2019. PMID: 30875857 Free PMC article. Review.
Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene expression. Studies in primary cultures of human CF airway epithelia and CF animal models demonstrate the long-term correction of CF phenoty …
Lentiviral vectors are well-suited for this purpose because they transduce nondividing cells, and provide long-term transgene express …
A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.
Montoro DT, Haber AL, Biton M, Vinarsky V, Lin B, Birket SE, Yuan F, Chen S, Leung HM, Villoria J, Rogel N, Burgin G, Tsankov AM, Waghray A, Slyper M, Waldman J, Nguyen L, Dionne D, Rozenblatt-Rosen O, Tata PR, Mou H, Shivaraju M, Bihler H, Mense M, Tearney GJ, Rowe SM, Engelhardt JF, Regev A, Rajagopal J. Montoro DT, et al. Nature. 2018 Aug;560(7718):319-324. doi: 10.1038/s41586-018-0393-7. Epub 2018 Aug 1. Nature. 2018. PMID: 30069044 Free PMC article.
We identify a rare cell type, the Foxi1(+) pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. …
We identify a rare cell type, the Foxi1(+) pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell …
Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.
Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, Zhang B, Solomon GM, Turner B, Bihler H, Harrington J, Lapey A, Channick C, Keyes C, Freund A, Artandi S, Mense M, Rowe S, Engelhardt JF, Hsu YC, Rajagopal J. Mou H, et al. Cell Stem Cell. 2016 Aug 4;19(2):217-231. doi: 10.1016/j.stem.2016.05.012. Epub 2016 Jun 16. Cell Stem Cell. 2016. PMID: 27320041 Free PMC article.