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Current Gene Therapy

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ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

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Review Article

Perspectives on Genetic Medicine for Cystic Fibrosis

Author(s): Svetlana A. Smirnikhina*

Volume 22, Issue 5, 2022

Published on: 05 August, 2022

Page: [386 - 396] Pages: 11

DOI: 10.2174/1566523222666220720102556

Price: $65

Abstract

Like any inherited protein deficiency disease, cystic fibrosis (CF) is a good candidate for gene replacement therapy. Despite the tremendous efforts of scientists worldwide invested in developing this approach, it did not lead to the expected results for various reasons discussed in this review. At the same time, the emergence of new methods of genome editing, as well as their latest modifications, makes it possible to bypass some of the problems of “classical” CF gene therapy. The review examines potential therapeutic agents for CF gene therapy, methods and routes of delivery, as well as discusses the problem of target cells for defect correction. Based on the results of these studies, editing genetic defects in the basal cells of the lungs and their counterparts in other organs will make it possible to create a drug for treating CF with a single administration.

Keywords: Cystic fibrosis, CFTR, gene therapy, genome editing, basal cells, viral vectors.

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Graphical Abstract

[1]
Bierlaagh MC, Muilwijk D, Beekman JM, van der Ent CK. A new era for people with cystic fibrosis. Eur J Pediatr 2021; 180(9): 2731-9.
[http://dx.doi.org/10.1007/s00431-021-04168-y] [PMID: 34213646]
[2]
The Clinical and Functional TRanslation of CFTR (CFTR2) 2021. Available from http://cftr2.org (Accessed: Nov 29 2021).
[3]
Amelina EL, Kashirskaya NYu, Kondratyeva EI, Krasovsky SA, Starinova MA, Voronkova AY. Register of patients with cystic fibrosis in the Russian Federation MEDPRACTICA-M 2020.
[4]
Bosch B, De Boeck K. Searching for a cure for cystic fibrosis. A 25-year quest in a nutshell. Eur J Pediatr 2016; 175(1): 1-8.
[http://dx.doi.org/10.1007/s00431-015-2664-8] [PMID: 26567541]
[5]
Van Goor F, Hadida S, Grootenhuis PD, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA 2009; 106(44): 18825-30.
[http://dx.doi.org/10.1073/pnas.0904709106] [PMID: 19846789]
[6]
FDA. KALYDECO, Patient Information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203188s019lbl.pdf(Accessed: Nov 29 2021).
[7]
Flume PA, Liou TG, Borowitz DS, et al. VX 08-770-104 Study Group. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest 2012; 142(3): 718-24.
[http://dx.doi.org/10.1378/chest.11-2672] [PMID: 22383668]
[8]
Sagel SD, Khan U, Heltshe SL, et al. Clinical effectiveness of lumacaftor/ivacaftor in patients with cystic fibrosis homozygous for F508del-CFTR. A clinical trial. Ann Am Thorac Soc 2021; 18(1): 75-83.
[http://dx.doi.org/10.1513/AnnalsATS.202002-144OC] [PMID: 32644818]
[9]
Griese M, Costa S, Linnemann RW, et al. Safety and efficacy of elexacaftor/tezacaftor/ivacaftor for 24 weeks or longer in people with cystic fibrosis and one or more F508del alleles: Interim results of an open-label phase 3 clinical trial. Am J Respir Crit Care Med 2021; 203(3): 381-5.
[http://dx.doi.org/10.1164/rccm.202008-3176LE] [PMID: 32969708]
[10]
Burgel PR, Munck A, Durieu I, et al. Real-life safety and effectiveness of lumacaftor-ivacaftor in patients with cystic fibrosis. Am J Respir Crit Care Med 2020; 201(2): 188-97.
[http://dx.doi.org/10.1164/rccm.201906-1227OC] [PMID: 31601120]
[11]
Aposhian HV. The use of DNA for gene therapy-the need, experimental approach, and implications. Perspect Biol Med 1970; 14(1): 98-108.
[http://dx.doi.org/10.1353/pbm.1970.0011] [PMID: 4321470]
[12]
Collins FS, Riordan JR, Tsui LC. The cystic fibrosis gene: Isolation and significance. Hosp Pract (Off Ed) 1990; 25(10): 47-57.
[http://dx.doi.org/10.1080/21548331.1990.11704019] [PMID: 1698801]
[13]
Aitken ML, Moss RB, Waltz DA, et al. A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease. Hum Gene Ther 2001; 12(15): 1907-16.
[http://dx.doi.org/10.1089/104303401753153956] [PMID: 11589832]
[14]
Flotte TR, Zeitlin PL, Reynolds TC, et al. Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: A two-part clinical study. Hum Gene Ther 2003; 14(11): 1079-88.
[http://dx.doi.org/10.1089/104303403322124792] [PMID: 12885347]
[15]
Flotte TR, Schwiebert EM, Zeitlin PL, Carter BJ, Guggino WB. Correlation between DNA transfer and cystic fibrosis airway epithelial cell correction after recombinant adeno-associated virus serotype 2 gene therapy. Hum Gene Ther 2005; 16(8): 921-8.
[http://dx.doi.org/10.1089/hum.2005.16.921] [PMID: 16076250]
[16]
Alton EW, Boyd AC, Davies JC, et al. Genetic medicines for CF: Hype versus reality. Pediatr Pulmonol 2016; 51(S44): S5-S17.
[http://dx.doi.org/10.1002/ppul.23543] [PMID: 27662105]
[17]
Cox DB, Platt RJ, Zhang F. Therapeutic genome editing: Prospects and challenges. Nat Med 2015; 21(2): 121-31.
[http://dx.doi.org/10.1038/nm.3793] [PMID: 25654603]
[18]
Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 2016; 533(7603): 420-4.
[http://dx.doi.org/10.1038/nature17946] [PMID: 27096365]
[19]
Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 2019; 576(7785): 149-57.
[http://dx.doi.org/10.1038/s41586-019-1711-4] [PMID: 31634902]
[20]
Alton EWFW, Armstrong DK, Ashby D, et al. A randomised, double-blind, placebo-controlled trial of repeated nebulisation of non-viral cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy in patients with cystic fibrosis. Southampton, UK: NIHR Journals Library 2016.
[http://dx.doi.org/10.3310/eme03050]
[21]
Haque AKMA, Dewerth A, Antony JS, et al. Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis. Sci Rep 2018; 8(1): 16776.
[http://dx.doi.org/10.1038/s41598-018-34960-0] [PMID: 30425265]
[22]
Yang E, van Nimwegen E, Zavolan M, et al. Decay rates of human mRNAs: Correlation with functional characteristics and sequence attributes. Genome Res 2003; 13(8): 1863-72.
[http://dx.doi.org/10.1101/gr.1272403] [PMID: 12902380]
[23]
Sasaki A, Kinjo M. Monitoring intracellular degradation of exogenous DNA using diffusion properties. J Control Release 2010; 143(1): 104-11.
[http://dx.doi.org/10.1016/j.jconrel.2009.12.013] [PMID: 20035810]
[24]
Brommel CM, Cooney AL, Sinn PL. Adeno-associated virus-based gene therapy for lifelong correction of genetic disease. Hum Gene Ther 2020; 31(17-18): 985-95.
[http://dx.doi.org/10.1089/hum.2020.138] [PMID: 32718227]
[25]
Griesenbach U, Pytel KM, Alton EW. Cystic fibrosis gene therapy in the UK and elsewhere. Hum Gene Ther 2015; 26(5): 266-75.
[http://dx.doi.org/10.1089/hum.2015.027] [PMID: 25838137]
[26]
Alton EW, Beekman JM, Boyd AC, et al. Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis. Thorax 2017; 72(2): 137-47.
[http://dx.doi.org/10.1136/thoraxjnl-2016-208406] [PMID: 27852956]
[27]
Ramalingam S, London V, Kandavelou K, et al. Generation and genetic engineering of human induced pluripotent stem cells using designed zinc finger nucleases. Stem Cells Dev 2013; 22(4): 595-610.
[http://dx.doi.org/10.1089/scd.2012.0245] [PMID: 22931452]
[28]
Yang R, Kerschner JL, Gosalia N, et al. Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus. Nucleic Acids Res 2016; 44(7): 3082-94.
[http://dx.doi.org/10.1093/nar/gkv1358] [PMID: 26673704]
[29]
Würtele H, Little KC, Chartrand P. Illegitimate DNA integration in mammalian cells. Gene Ther 2003; 10(21): 1791-9.
[http://dx.doi.org/10.1038/sj.gt.3302074] [PMID: 12960968]
[30]
Smirnov A, Fishman V, Yunusova A, et al. DNA barcoding reveals that injected transgenes are predominantly processed by homologous recombination in mouse zygote. Nucleic Acids Res 2020; 48(2): 719-35.
[PMID: 31740957]
[31]
Jabalameli HR, Zahednasab H, Karimi-Moghaddam A, Jabalameli MR. Zinc finger nuclease technology: Advances and obstacles in modelling and treating genetic disorders. Gene 2015; 558(1): 1-5.
[http://dx.doi.org/10.1016/j.gene.2014.12.044] [PMID: 25536166]
[32]
Wright DA, Li T, Yang B, Spalding MH. TALEN-mediated genome editing: Prospects and perspectives. Biochem J 2014; 462(1): 15-24.
[http://dx.doi.org/10.1042/BJ20140295] [PMID: 25057889]
[33]
Fellmann C, Gowen BG, Lin PC, Doudna JA, Corn JE. Cornerstones of CRISPR-Cas in drug discovery and therapy. Nat Rev Drug Discov 2017; 16(2): 89-100.
[http://dx.doi.org/10.1038/nrd.2016.238] [PMID: 28008168]
[34]
Nishida K, Arazoe T, Yachie N, et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 2016; 353(6305): aaf8729.
[http://dx.doi.org/10.1126/science.aaf8729] [PMID: 27492474]
[35]
Gaudelli NM, Komor AC, Rees HA, et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 2017; 551(7681): 464-71.
[http://dx.doi.org/10.1038/nature24644] [PMID: 29160308]
[36]
Hess GT, Frésard L, Han K, et al. Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat Methods 2016; 13(12): 1036-42.
[http://dx.doi.org/10.1038/nmeth.4038] [PMID: 27798611]
[37]
McNeer NA, Anandalingam K, Fields RJ, et al. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nat Commun 2015; 6(1): 6952.
[http://dx.doi.org/10.1038/ncomms7952] [PMID: 25914116]
[38]
Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 2017; 18(8): 495-506.
[http://dx.doi.org/10.1038/nrm.2017.48] [PMID: 28512351]
[39]
Liu M, Rehman S, Tang X, et al. Methodologies for improving HDR efficiency. Front Genet 2019; 9: 691.
[http://dx.doi.org/10.3389/fgene.2018.00691] [PMID: 30687381]
[40]
Suzuki S, Sargent RG, Illek B, et al. TALENs facilitate single-step seamless SDF correction of F508del CFTR in airway epithelial submucosal gland cell-derived CF-iPSCs. Mol Ther Nucleic Acids 2016; 5(1): e273.
[http://dx.doi.org/10.1038/mtna.2015.43] [PMID: 26730810]
[41]
Maule G, Casini A, Montagna C, et al. Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing. Nat Commun 2019; 10(1): 3556.
[http://dx.doi.org/10.1038/s41467-019-11454-9] [PMID: 31391465]
[42]
Bednarski C, Tomczak K, Vom Hövel B, Weber WM, Cathomen T. Targeted integration of a super-exon into the CFTR locus leads to functional correction of a cystic fibrosis cell line model. PLoS One 2016; 11(8): e0161072.
[http://dx.doi.org/10.1371/journal.pone.0161072] [PMID: 27526025]
[43]
Firth AL, Menon T, Parker GS, et al. Functional gene correction for cystic fibrosis in lung epithelial cells generated from patient iPSCs. Cell Rep 2015; 12(9): 1385-90.
[http://dx.doi.org/10.1016/j.celrep.2015.07.062] [PMID: 26299960]
[44]
Smirnikhina SA, Kondrateva EV, Adilgereeva EP, et al. P.F508del editing in cells from cystic fibrosis patients. PLoS One 2020; 15(11): e0242094.
[http://dx.doi.org/10.1371/journal.pone.0242094] [PMID: 33175893]
[45]
Ruan J, Hirai H, Yang D, et al. Efficient gene editing at major CFTR mutation loci. Mol Ther Nucleic Acids 2019; 16: 73-81.
[http://dx.doi.org/10.1016/j.omtn.2019.02.006] [PMID: 30852378]
[46]
Vaidyanathan S, Salahudeen AA, Sellers ZM, et al. High-efficiency, selection-free gene repair in airway stem cells from cystic fibrosis patients rescues CFTR function in differentiated epithelia. Cell Stem Cell 2020; 26(2): 161-171.e4.
[http://dx.doi.org/10.1016/j.stem.2019.11.002] [PMID: 31839569]
[47]
Smirnikhina SA, Anuchina AA, Lavrov AV. Ways of improving precise knock-in by genome-editing technologies. Hum Genet 2019; 138(1): 1-19.
[http://dx.doi.org/10.1007/s00439-018-1953-5] [PMID: 30390160]
[48]
Adikusuma F, Piltz S, Corbett MA, et al. Large deletions induced by Cas9 cleavage. Nature 2018; 560(7717): E8-9.
[http://dx.doi.org/10.1038/s41586-018-0380-z] [PMID: 30089922]
[49]
Geurts MH, de Poel E, Amatngalim GD, et al. CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank. Cell Stem Cell 2020; 26(4): 503-510.e7.
[http://dx.doi.org/10.1016/j.stem.2020.01.019] [PMID: 32084388]
[50]
Smirnikhina SA. Prime editing: Making the move to prime time. CRISPR J 2020; 3(5): 319-21.
[http://dx.doi.org/10.1089/crispr.2020.29105.sas] [PMID: 33095049]
[51]
Geurts MH, de Poel E, Pleguezuelos-Manzano C, et al. Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in organoids. Life Sci Alliance 2021; 4(10): e202000940.
[http://dx.doi.org/10.26508/lsa.202000940] [PMID: 34373320]
[52]
Rogers FA, Vasquez KM, Egholm M, Glazer PM. Site-directed recombination via bifunctional PNA-DNA conjugates. Proc Natl Acad Sci USA 2002; 99(26): 16695-700.
[http://dx.doi.org/10.1073/pnas.262556899] [PMID: 12461167]
[53]
Drevinek P, Pressler T, Cipolli M, et al. Antisense oligonucleotide eluforsen is safe and improves respiratory symptoms in F508DEL cystic fibrosis. J Cyst Fibros 2020; 19(1): 99-107.
[http://dx.doi.org/10.1016/j.jcf.2019.05.014] [PMID: 31182369]
[54]
Sermet-Gaudelus I, Clancy JP, Nichols DP, et al. Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis. J Cyst Fibros 2019; 18(4): 536-42.
[http://dx.doi.org/10.1016/j.jcf.2018.10.015] [PMID: 30467074]
[55]
Suzuki S, Crane AM, Anirudhan V, et al. Highly efficient gene editing of cystic fibrosis patient-derived airway basal cells results in functional CFTR correction. Mol Ther 2020; 28(7): 1684-95.
[http://dx.doi.org/10.1016/j.ymthe.2020.04.021] [PMID: 32402246]
[56]
Santos L, Mention K, Cavusoglu-Doran K, et al. Comparison of Cas9 and Cas12a CRISPR editing methods to correct the W1282X-CFTR mutation. J Cyst Fibros 2022; 21(1): 181-7.
[http://dx.doi.org/10.1016/j.jcf.2021.05.014] [PMID: 34103250]
[57]
Ringer KP, Roth MG, Garey MS, et al. Comparative analysis of lipid-mediated CRISPR-Cas9 genome editing techniques. Cell Biol Int 2018; 42(7): 849-58.
[http://dx.doi.org/10.1002/cbin.10952] [PMID: 29457665]
[58]
Liu X, Jiang Q, Mansfield SG, et al. Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing. Nat Biotechnol 2002; 20(1): 47-52.
[http://dx.doi.org/10.1038/nbt0102-47] [PMID: 11753361]
[59]
Liu X, Luo M, Zhang LN, et al. Spliceosome-mediated RNA trans-splicing with recombinant adeno-associated virus partially restores cystic fibrosis transmembrane conductance regulator function to polarized human cystic fibrosis airway epithelial cells. Hum Gene Ther 2005; 16(9): 1116-23.
[http://dx.doi.org/10.1089/hum.2005.16.1116] [PMID: 16149910]
[60]
Hong EM, Ingemarsdotter CK, Lever AML. Therapeutic applications of trans-splicing. Br Med Bull 2020; 136(1): 4-20.
[http://dx.doi.org/10.1093/bmb/ldaa028] [PMID: 33010155]
[61]
Wally V, Murauer EM, Bauer JW. Spliceosome-mediated trans-splicing: The therapeutic cut and paste. J Invest Dermatol 2012; 132(8): 1959-66.
[http://dx.doi.org/10.1038/jid.2012.101] [PMID: 22495179]
[62]
Berger A, Maire S, Gaillard MC, Sahel JA, Hantraye P, Bemelmans AP. mRNA trans-splicing in gene therapy for genetic diseases. Wiley Interdiscip Rev RNA 2016; 7(4): 487-98.
[http://dx.doi.org/10.1002/wrna.1347] [PMID: 27018401]
[63]
Gillen AE, Gosalia N, Leir SH, Harris A. MicroRNA regulation of expression of the cystic fibrosis transmembrane conductance regulator gene. Biochem J 2011; 438(1): 25-32.
[http://dx.doi.org/10.1042/BJ20110672] [PMID: 21689072]
[64]
Fabbri E, Tamanini A, Jakova T, et al. A peptide nucleic acid against microRNA miR-145-5p enhances the expression of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Calu-3 cells. Molecules 2017; 23(1): 71.
[http://dx.doi.org/10.3390/molecules23010071] [PMID: 29286300]
[65]
Sultan S, Rozzi A, Gasparello J, et al. A Peptide Nucleic Acid (PNA) Masking the miR-145-5p binding site of the 3'UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA enhances CFTR expression in Calu-3 cells. Molecules 2020; 25(7): 1677.
[http://dx.doi.org/10.3390/molecules25071677] [PMID: 32260566]
[66]
Fabbri E, Tamanini A, Jakova T, et al. Treatment of human airway epithelial Calu-3 cells with a peptide-nucleic acid (PNA) targeting the microRNA miR-101-3p is associated with increased expression of the cystic fibrosis Transmembrane Conductance Regulator () gene. Eur J Med Chem 2021; 209: 112876.
[http://dx.doi.org/10.1016/j.ejmech.2020.112876] [PMID: 33127171]
[67]
Tamanini A, Fabbri E, Jakova T, et al. A peptide-nucleic acid targeting miR-335-5p enhances expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene with the possible involvement of the CFTR scaffolding protein NHERF1. Biomedicines 2021; 9(2): 117.
[http://dx.doi.org/10.3390/biomedicines9020117] [PMID: 33530577]
[68]
Boucher RC, Knowles MR, Johnson LG, et al. Gene therapy for cystic fibrosis using E1-deleted adenovirus: A phase I trial in the nasal cavity. Hum Gene Ther 1994; 5(5): 615-39.
[http://dx.doi.org/10.1089/hum.1994.5.5-615] [PMID: 7519885]
[69]
Knowles MR, Hohneker KW, Zhou Z, et al. A controlled study of adenoviral-vector-mediated gene transfer in the nasal epithelium of patients with cystic fibrosis. N Engl J Med 1995; 333(13): 823-31.
[http://dx.doi.org/10.1056/NEJM199509283331302] [PMID: 7544439]
[70]
Zuckerman JB, Robinson CB, McCoy KS, et al. A phase I study of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator gene to a lung segment of individuals with cystic fibrosis. Hum Gene Ther 1999; 10(18): 2973-85.
[http://dx.doi.org/10.1089/10430349950016384] [PMID: 10609658]
[71]
Moss RB, Rodman D, Spencer LT, et al. Repeated adeno-associated virus serotype 2 aerosol-mediated cystic fibrosis transmembrane regulator gene transfer to the lungs of patients with cystic fibrosis: A multicenter, double-blind, placebo-controlled trial. Chest 2004; 125(2): 509-21.
[http://dx.doi.org/10.1378/chest.125.2.509] [PMID: 14769732]
[72]
Davies LA, Nunez-Alonso GA, McLachlan G, Hyde SC, Gill DR. Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy. Hum Gene Ther Clin Dev 2014; 25(2): 97-107.
[http://dx.doi.org/10.1089/humc.2014.019] [PMID: 24865497]
[73]
Alton EWFW, Armstrong DK, Ashby D, et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: A randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med 2015; 3(9): 684-91.
[http://dx.doi.org/10.1016/S2213-2600(15)00245-3] [PMID: 26149841]
[74]
Cmielewski P, Farrow N, Devereux S, Parsons D, Donnelley M. Gene therapy for Cystic Fibrosis: Improved delivery techniques and conditioning with lysophosphatidylcholine enhance lentiviral gene transfer in mouse lung airways. Exp Lung Res 2017; 43(9-10): 426-33.
[http://dx.doi.org/10.1080/01902148.2017.1395931] [PMID: 29236544]
[75]
Robinson E, MacDonald KD, Slaughter K, et al. Lipid nanoparticle-delivered chemically modified mRNA restores chloride secretion in cystic fibrosis. Mol Ther 2018; 26(8): 2034-46.
[http://dx.doi.org/10.1016/j.ymthe.2018.05.014] [PMID: 29910178]
[76]
Reyne N, Cmielewski P, McCarron A, Delhove J, Parsons D, Donnelley M. Single-dose lentiviral mediated gene therapy recovers CFTR function in cystic fibrosis knockout rats. Front Pharmacol 2021; 12: 682299.
[http://dx.doi.org/10.3389/fphar.2021.682299] [PMID: 34084147]
[77]
Schuster BS, Kim AJ, Kays JC, et al. Overcoming the cystic fibrosis sputum barrier to leading adeno-associated virus gene therapy vectors. Mol Ther 2014; 22(8): 1484-93.
[http://dx.doi.org/10.1038/mt.2014.89] [PMID: 24869933]
[78]
Hida K, Lai SK, Suk JS, Won SY, Boyle MP, Hanes J. Common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients. PLoS One 2011; 6(5): e19919.
[http://dx.doi.org/10.1371/journal.pone.0019919] [PMID: 21637751]
[79]
Schuster BS, Suk JS, Woodworth GF, Hanes J. Nanoparticle diffusion in respiratory mucus from humans without lung disease. Biomaterials 2013; 34(13): 3439-46.
[http://dx.doi.org/10.1016/j.biomaterials.2013.01.064] [PMID: 23384790]
[80]
Limberis M, Anson DS, Fuller M, Parsons DW. Recovery of airway cystic fibrosis transmembrane conductance regulator function in mice with cystic fibrosis after single-dose lentivirus-mediated gene transfer. Hum Gene Ther 2002; 13(16): 1961-70.
[http://dx.doi.org/10.1089/10430340260355365] [PMID: 12427306]
[81]
Stocker AG, Kremer KL, Koldej R, Miller DS, Anson DS, Parsons DW. Single-dose lentiviral gene transfer for lifetime airway gene expression. J Gene Med 2009; 11(10): 861-7.
[http://dx.doi.org/10.1002/jgm.1368] [PMID: 19634193]
[82]
Rosen BH, Chanson M, Gawenis LR, et al. Animal and model systems for studying cystic fibrosis. J Cyst Fibros 2018; 17(2S): S28-34.
[http://dx.doi.org/10.1016/j.jcf.2017.09.001] [PMID: 28939349]
[83]
Farrow N, Cmielewski P, Delhove J, et al. Towards human translation of lentiviral airway gene delivery for cystic fibrosis: A one-month CFTR and reporter gene study in marmosets. Hum Gene Ther 2021; 32(15-16): 806-16.
[http://dx.doi.org/10.1089/hum.2020.267] [PMID: 33446042]
[84]
Cooney AL, Singh BK, Loza LM, et al. Widespread airway distribution and short-term phenotypic correction of cystic fibrosis pigs following aerosol delivery of piggyBac/adenovirus. Nucleic Acids Res 2018; 46(18): 9591-600.
[http://dx.doi.org/10.1093/nar/gky773] [PMID: 30165523]
[85]
Edmondson C, Davies JC. Current and future treatment options for cystic fibrosis lung disease: Latest evidence and clinical implications. Ther Adv Chronic Dis 2016; 7(3): 170-83.
[http://dx.doi.org/10.1177/2040622316641352] [PMID: 27347364]
[86]
Parekh KR, Nawroth J, Pai A, Busch SM, Senger CN, Ryan AL. Stem cells and lung regeneration. Am J Physiol Cell Physiol 2020; 319(4): C675-93.
[http://dx.doi.org/10.1152/ajpcell.00036.2020] [PMID: 32783658]
[87]
Bustamante-Marin XM, Ostrowski LE. Cilia and mucociliary clearance. Cold Spring Harb Perspect Biol 2017; 9(4): a028241.
[http://dx.doi.org/10.1101/cshperspect.a028241] [PMID: 27864314]
[88]
Katz MG, Fargnoli AS, Gubara SM, et al. Targeted gene delivery through the respiratory system: Rationale for intratracheal gene transfer. J Cardiovasc Dev Dis 2019; 6(1): 8.
[http://dx.doi.org/10.3390/jcdd6010008] [PMID: 30781363]
[89]
Peng KW, Pham L, Ye H, et al. Organ distribution of gene expression after intravenous infusion of targeted and untargeted lentiviral vectors. Gene Ther 2001; 8(19): 1456-63.
[http://dx.doi.org/10.1038/sj.gt.3301552] [PMID: 11593358]
[90]
Hiltunen MO, Turunen MP, Turunen AM, et al. Biodistribution of adenoviral vector to nontarget tissues after local in vivo gene transfer to arterial wall using intravascular and periadventitial gene delivery methods. FASEB J 2000; 14(14): 2230-6.
[http://dx.doi.org/10.1096/fj.00-0145com] [PMID: 11053244]
[91]
McCaskill J, Singhania R, Burgess M, et al. Efficient biodistribution and gene silencing in the lung epithelium via intravenous liposomal delivery of siRNA. Mol Ther Nucleic Acids 2013; 2(6): e96.
[http://dx.doi.org/10.1038/mtna.2013.22] [PMID: 23736774]
[92]
Michelfelder S, Varadi K, Raupp C, et al. Peptide ligands incorporated into the threefold spike capsid domain to re-direct gene transduction of AAV8 and AAV9 in vivo. PLoS One 2011; 6(8): e23101.
[http://dx.doi.org/10.1371/journal.pone.0023101] [PMID: 21850255]
[93]
Wu P, Xiao W, Conlon T, et al. Mutational analysis of the Adeno-Associated Virus type 2 (AAV2) capsid gene and construction of AAV2 vectors with altered tropism. J Virol 2000; 74(18): 8635-47.
[http://dx.doi.org/10.1128/JVI.74.18.8635-8647.2000] [PMID: 10954565]
[94]
Johnson M, Huyn S, Burton J, Sato M, Wu L. Differential biodistribution of adenoviral vector in vivo as monitored by bioluminescence imaging and quantitative polymerase chain reaction. Hum Gene Ther 2006; 17(12): 1262-9.
[http://dx.doi.org/10.1089/hum.2006.17.1262] [PMID: 17117891]
[95]
Kochergin-Nikitsky K, Belova L, Lavrov A, Smirnikhina S. Tissue and cell-type-specific transduction using rAAV vectors in lung diseases. J Mol Med (Berl) 2021; 99(8): 1057-71.
[http://dx.doi.org/10.1007/s00109-021-02086-y] [PMID: 34021360]
[96]
Marquez Loza LI, Yuen EC, McCray PB Jr. Lentiviral vectors for the treatment and prevention of cystic fibrosis lung disease. Genes (Basel) 2019; 10(3): 218.
[http://dx.doi.org/10.3390/genes10030218] [PMID: 30875857]
[97]
Johnson LG. Retroviral approaches to gene therapy of cystic fibrosis Ann N Y Acad Sci 2001; 953(1 NEW VISTAS IN): 43-52.
[http://dx.doi.org/10.1111/j.1749-6632.2001.tb11359.x] [PMID: 11795422]
[98]
Brody SL, Crystal RG. Adenovirus-mediated in vivo gene transfer. Ann N Y Acad Sci 1994; 716: 90-101.
[http://dx.doi.org/10.1111/j.1749-6632.1994.tb21705.x] [PMID: 7517653]
[99]
Van Heeckeren AM, Scaria A, Schluchter MD, Ferkol TW, Wadsworth S, Davis PB. Delivery of CFTR by adenoviral vector to cystic fibrosis mouse lung in a model of chronic Pseudomonas aeruginosa lung infection. Am J Physiol Lung Cell Mol Physiol 2004; 286(4): L717-26.
[http://dx.doi.org/10.1152/ajplung.00227.2003] [PMID: 14514520]
[100]
Cao H, Ouyang H, Laselva O, et al. A helper-dependent adenoviral vector rescues CFTR to wild-type functional levels in cystic fibrosis epithelial cells harbouring class I mutations. Eur Respir J 2020; 56(5): 2000205.
[http://dx.doi.org/10.1183/13993003.00205-2020] [PMID: 32457197]
[101]
Martini SV, Rocco PR, Morales MM. Adeno-associated virus for cystic fibrosis gene therapy. Braz J Med Biol Res 2011; 44(11): 1097-104.
[http://dx.doi.org/10.1590/S0100-879X2011007500123] [PMID: 21952739]
[102]
Palmer DJ, Turner DL, Ng PA. Single “All-in-One” helper-dependent adenovirus to deliver donor DNA and CRISPR/Cas9 for efficient homology-directed repair. Mol Ther Methods Clin Dev 2020; 17: 441-7.
[http://dx.doi.org/10.1016/j.omtm.2020.01.014] [PMID: 32154329]
[103]
Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118(9): 3132-42.
[http://dx.doi.org/10.1172/JCI35700] [PMID: 18688285]
[104]
Themis M, Waddington SN, Schmidt M, et al. Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice. Mol Ther 2005; 12(4): 763-71.
[http://dx.doi.org/10.1016/j.ymthe.2005.07.358] [PMID: 16084128]
[105]
Cooney AL, Abou Alaiwa MH, Shah VS, et al. Lentiviral-mediated phenotypic correction of cystic fibrosis pigs. JCI Insight 2016; 1(14): e88730.
[http://dx.doi.org/10.1172/jci.insight.88730] [PMID: 27656681]
[106]
Welsh MJ, Smith AE, Zabner J, et al. Cystic fibrosis gene therapy using an adenovirus vector: In vivo safety and efficacy in nasal epithelium. Hum Gene Ther 1994; 5(2): 209-19.
[http://dx.doi.org/10.1089/hum.1994.5.2-209] [PMID: 7514450]
[107]
Khare R, Chen CY, Weaver EA, Barry MA. Advances and future challenges in adenoviral vector pharmacology and targeting. Curr Gene Ther 2011; 11(4): 241-58.
[http://dx.doi.org/10.2174/156652311796150363] [PMID: 21453281]
[108]
Shibata M, Nishimasu H, Kodera N, et al. Real-space and real-time dynamics of CRISPR-Cas9 visualized by high-speed atomic force microscopy. Nat Commun 2017; 8(1): 1430.
[http://dx.doi.org/10.1038/s41467-017-01466-8] [PMID: 29127285]
[109]
Sibbald B. Death but one unintended consequence of gene-therapy trial. CMAJ 2001; 164(11): 1612.
[PMID: 11402803]
[110]
Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: Two open, non-randomised phase 1/2 studies from Russia. Lancet 2020; 396(10255): 887-97.
[http://dx.doi.org/10.1016/S0140-6736(20)31866-3] [PMID: 32896291]
[111]
Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021; 397(10275): 671-81.
[http://dx.doi.org/10.1016/S0140-6736(21)00234-8] [PMID: 33545094]
[112]
Flotte TR, Afione SA, Conrad C, et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc Natl Acad Sci USA 1993; 90(22): 10613-7.
[http://dx.doi.org/10.1073/pnas.90.22.10613] [PMID: 7504271]
[113]
Vidović D, Carlon MS, da Cunha MF, et al. rAAV-CFTRΔR rescues the cystic fibrosis phenotype in human intestinal organoids and cystic fibrosis mice. Am J Respir Crit Care Med 2016; 193(3): 288-98.
[http://dx.doi.org/10.1164/rccm.201505-0914OC] [PMID: 26509335]
[114]
Fischer AC, Smith CI, Cebotaru L, et al. Expression of a truncated cystic fibrosis transmembrane conductance regulator with an AAV5-pseudotyped vector in primates. Mol Ther 2007; 15(4): 756-63.
[http://dx.doi.org/10.1038/sj.mt.6300059] [PMID: 17299412]
[115]
Patel A, Zhao J, Duan D, Lai Y. Design of AAV vectors for delivery of large or multiple transgenes. Methods Mol Biol 2019; 1950: 19-33.
[http://dx.doi.org/10.1007/978-1-4939-9139-6_2] [PMID: 30783966]
[116]
Kristen AV, Ajroud-Driss S, Conceição I, Gorevic P, Kyriakides T, Obici L. Patisiran, an RNAi therapeutic for the treatment of hereditary transthyretin-mediated amyloidosis. Neurodegener Dis Manag 2019; 9(1): 5-23.
[http://dx.doi.org/10.2217/nmt-2018-0033] [PMID: 30480471]
[117]
Alfano LN, Charleston JS, Connolly AM, et al. Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy. Medicine (Baltimore) 2019; 98(26): e15858.
[http://dx.doi.org/10.1097/MD.0000000000015858] [PMID: 31261494]
[118]
Hu J, Sheng Y, Shi J, Yu B, Yu Z, Liao G. Long circulating polymeric nanoparticles for gene/drug delivery. Curr Drug Metab 2018; 19(9): 723-38.
[http://dx.doi.org/10.2174/1389200219666171207120643] [PMID: 29219050]
[119]
Fernández Fernández E, Santos-Carballal B, de Santi C, et al. Biopolymer-based nanoparticles for cystic fibrosis lung gene therapy studies. Materials (Basel) 2018; 11(1): 122.
[http://dx.doi.org/10.3390/ma11010122] [PMID: 29342838]
[120]
Kolonko AK, Efing J, González-Espinosa Y, et al. Capsaicin-loaded chitosan nanocapsules for wtCFTR-mRNA delivery to a cystic fibrosis cell line. Biomedicines 2020; 8(9): 364.
[http://dx.doi.org/10.3390/biomedicines8090364] [PMID: 32962254]
[121]
Singh BK, Cooney AL, Krishnamurthy S, Sinn PL. Extracellular vesicle-mediated sirna delivery, protein delivery, and CFTR complementation in well-differentiated human airway epithelial cells. Genes (Basel) 2020; 11(4): 351.
[http://dx.doi.org/10.3390/genes11040351] [PMID: 32224868]
[122]
Bell GD, Yang Y, Leung E, Krissansen GW. mRNA transfection by a Xentry-protamine cell-penetrating peptide is enhanced by TLR antagonist E6446. PLoS One 2018; 13(7): e0201464.
[http://dx.doi.org/10.1371/journal.pone.0201464] [PMID: 30059522]
[123]
Xie J, Bi Y, Zhang H, et al. Cell-penetrating peptides in diagnosis and treatment of human diseases: From preclinical research to clinical application. Front Pharmacol 2020; 11: 697.
[http://dx.doi.org/10.3389/fphar.2020.00697] [PMID: 32508641]
[124]
Vituret C, Gallay K, Confort MP, et al. Transfer of the cystic fibrosis transmembrane conductance regulator to human cystic fibrosis cells mediated by extracellular vesicles. Hum Gene Ther 2016; 27(2): 166-83.
[http://dx.doi.org/10.1089/hum.2015.144] [PMID: 26886833]
[125]
Villamizar O, Waters SA, Scott T, Grepo N, Jaffe A, Morris KV. Mesenchymal Stem Cell exosome delivered Zinc Finger Protein activation of cystic fibrosis transmembrane conductance regulator. J Extracell Vesicles 2021; 10(3): e12053.
[http://dx.doi.org/10.1002/jev2.12053] [PMID: 33532041]
[126]
Plasschaert LW, Žilionis R, Choo-Wing R, et al. A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte. Nature 2018; 560(7718): 377-81.
[http://dx.doi.org/10.1038/s41586-018-0394-6] [PMID: 30069046]
[127]
Rawlins EL, Hogan BL. Ciliated epithelial cell lifespan in the mouse trachea and lung. Am J Physiol Lung Cell Mol Physiol 2008; 295(1): L231-4.
[http://dx.doi.org/10.1152/ajplung.90209.2008] [PMID: 18487354]
[128]
Hollywood JA, Lee CM, Scallan MF, Harrison PT. Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene. Sci Rep 2016; 6(1): 32230.
[http://dx.doi.org/10.1038/srep32230] [PMID: 27557525]
[129]
Deprez M, Zaragosi LE, Truchi M, et al. A single-cell atlas of the human healthy airways. Am J Respir Crit Care Med 2020; 202(12): 1636-45.
[http://dx.doi.org/10.1164/rccm.201911-2199OC] [PMID: 32726565]
[130]
Okuda K, Dang H, Kobayashi Y, et al. Secretory cells dominate airway CFTR expression and function in human airway superficial epithelia. Am J Respir Crit Care Med 2021; 203(10): 1275-89.
[http://dx.doi.org/10.1164/rccm.202008-3198OC] [PMID: 33321047]
[131]
Flotte TR. Airway basal cells are the key for cystic fibrosis gene therapy. Hum Gene Ther 2018; 29(6): 641-2.
[http://dx.doi.org/10.1089/hum.2018.29066.trf] [PMID: 29902084]
[132]
King NE, Suzuki S, Barillà C, et al. Correction of airway stem cells: Genome editing approaches for the treatment of cystic fibrosis. Hum Gene Ther 2020; 31(17-18): 956-72.
[http://dx.doi.org/10.1089/hum.2020.160] [PMID: 32741223]
[133]
Cao H, Ouyang H, Grasemann H, et al. Transducing airway basal cells with a helper-dependent adenoviral vector for lung gene therapy. Hum Gene Ther 2018; 29(6): 643-52.
[http://dx.doi.org/10.1089/hum.2017.201] [PMID: 29320887]

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