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Chapter 52 - Gene Therapy: Principles and Clinical Potential

from Gene Therapy

Published online by Cambridge University Press:  21 October 2019

By
Suzanne M. K. Buckley  and
Anna L. David
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
Mark D. Kilby
Affiliation:
University of Birmingham
Anthony Johnson
Affiliation:
University of Texas Medical School at Houston
Dick Oepkes
Affiliation:
Leids Universitair Medisch Centrum
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Summary

Gene therapy uses a vector to deliver a gene to its required site, where expression of the protein can produce a therapeutic effect. In the last decade there have been significant therapeutic breakthroughs, with clinical trials of postnatal gene therapy showing efficacy for a variety of diseases, such as hemophilia, congenital blindness, congenital immunodeficiency and neuromuscular disorders, and the first gene therapy for familial hyperlipidemia was approved in the European Union (EU) in 2012.

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 540 - 560
Publisher: Cambridge University Press
Print publication year: 2020

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References

Waddington, SN, Nivsarkar, MS, Mistry, AR, Buckley, SMK, Kemball-Cook, G, Mosley, KL, et al. Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy. Blood. 2004; 104: 2714–21.Google Scholar
Tran, ND, Porada, CD, Almeida-Porada, G, Glimp, HA, French Anderson, W, Zanjani, ED. Induction of stable prenatal tolerance to β-galactosidase by in utero gene transfer into preimmune sheep fetuses. Blood. 2001; 97: 3417–23.CrossRefGoogle ScholarPubMed
US National Institutes of Health Recombinant DNA Advisory Committee. Prenatal gene transfer: scientific, medical, and ethical issues: a report of the Recombinant DNA Advisory Committee. Hum Gene Ther. 2000; 11: 1211–29.Google Scholar
Sabatino, DE, MacKenzie, TC, Peranteau, W, Edmonson, S, Campagnoli, C, Liu, YL, et al. Persistent expression of hF.IX after tolerance induction by in utero or neonatal administration of AAV-1-F.IX in hemophilia B mice. Mol Ther. 2007; 15: 1677–85.Google Scholar
Porada, CD, Tran, N, Eglitis, M, Moen, RC, Troutman, L, Flake, AW, et al. In utero gene therapy: transfer and long-term expression of the bacterial neo(r) gene in sheep after direct injection of retroviral vectors into preimmune fetuses. Hum Gene Ther. 1998; 9: 1571–85.Google Scholar
Yang, EY, Cass, DL, Sylvester, KG, Wilson, JM, Adzick, NS. Fetal gene therapy: efficacy, toxicity, and immunologic effects of early gestation recombinant adenovirus. J Pediatr Surg. 1999; 34: 235–41.Google Scholar
David, A, Peebles, D, Miah, M, Themis, M, Nivsarkar, M, Tucker, N, et al. Ultrasound-guided delivery of viral vectors encoding the beta-galactosidase and human factor IX genes to early gestation fetal sheep in utero. Hum Gene Ther. 2002; 364: 353–64.Google Scholar
Nathwani, AC, Gray, JT, Ng, CYC, Zhou, J, Spence, Y, Waddington, SN, et al. Self-complementary adeno-associated virus vectors containing a novel liver-specific human factor IX expression cassette enable highly efficient transduction of murine and nonhuman primate liver. Blood. 2006; 107: 2653–61.Google Scholar
David, AL, McIntosh, J, Peebles, DM, Cook, T, Waddington, S, Weisz, B, et al. Recombinant adeno-associated virus-mediated in utero gene transfer gives therapeutic transgene expression in the sheep. Hum Gene Ther. 2011; 22: 419–26.Google Scholar
Mattar, C, Nathwani, A, Waddington, S, Dighe, N, Kaeppel, C, Nowrouzi, A, et al. Stable human FIX expression after 0.9G intrauterine gene transfer of self-complementary adeno-associated viral vector 5 and 8 in macaques. Mol Ther. 2011; 19: 1950–60.CrossRefGoogle ScholarPubMed
Mattar, CN, Gil-Farina, I, Rosales, C, Johana, N, Yi Wan Tan, Y, McIntosh, J, et al. In utero transfer of adeno-associated viral vectors produces long-term factor IX levels in a cynomolgus macaque model. Mol Ther. 2017; 25: 1843–53.Google Scholar
Mattar, CN, Wong, AMS, Hoefer, K, Alonso-Ferrero, ME, Buckley, SMK, Howe, SJ, et al. Systemic gene delivery following intravenous administration of AAV9 to fetal and neonatal mice and late-gestation nonhuman primates. FASEB J. 2015; 29: 3876–88.CrossRefGoogle ScholarPubMed
Nathwani, AC, Tuddenham, EGD, Rangarajan, S, Rosales, C, McIntosh, J, Linch, DC, et al. Adenovirus-associated virus vector–mediated gene transfer in hemophilia B. N Engl J Med. 2011; 365: 2357–65.Google Scholar
George, LA, Sullivan, SK, Giermasz, A, Rasko, JEJ, Samelson-Jones, BJ, Ducore, J, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. N Engl J Med. 2017; 377: 2215–27.Google Scholar
Rangarajan, S, Walsh, L, Lester, W, Perry, D, Madan, B, Laffan, M, et al. AAV5–Factor VIII gene transfer in severe hemophilia A. N Engl J Med. 2017; 377: 2519–30.Google Scholar
McVey, JH, Boswell, E, Mumford, AD, Kemball-Cook, G, Tuddenham, EG. Factor VII deficiency and the FVII mutation database. Hum Mutat. 2001; 17: 3–17.Google Scholar
Binny, C, McIntosh, J, Della Peruta, M, Kymalainen, H, Tuddenham, EGD, Buckley, SMK, et al. AAV-mediated gene transfer in the perinatal period results in expression of FVII at levels that protect against fatal spontaneous hemorrhage. Blood. 2012; 119: 957–66.CrossRefGoogle ScholarPubMed
Modell, B, Darlison, M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008; 86: 480–7.Google Scholar
Lucarelli, G, Isgrò, A, Sodani, P, Gaziev, J. Hematopoietic stem cell transplantation in thalassemia and sickle cell anemia. Cold Spring Harb Perspect Med. 2012; 2: a011825.CrossRefGoogle ScholarPubMed
Pawliuk, R, Westerman, KA, Fabry, ME, Payen, E, Tighe, R, Bouhassira, EE, et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science. 2001; 294: 2368–71.CrossRefGoogle ScholarPubMed
Rivella, S, May, C, Chadburn, A, Rivière, I, Sadelain, M. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human β-globin gene transfer. Blood. 2003; 101: 2932–9.CrossRefGoogle ScholarPubMed
Han, X-D, Lin, C, Chang, J, Sadelain, M, Kan, YW. Fetal gene therapy of alpha-thalassemia in a mouse model. Proc Natl Acad Sci U S A. 2007; 104: 907–11.Google Scholar
Cavazzana-Calvo, M, Payen, E, Negre, O, Wang, G, Hehir, K, Fusil, F, et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature. 2010; 467: 318–22.Google Scholar
Thompson, AA, Walters, MC, Kwiatkowski, J, et al. Gene therapy in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2018; 378: 1479–93.Google Scholar
Shaw, SWS, Blundell, MP, Pipino, C, Shangaris, P, Maghsoudlou, P, Ramachandra, DL, et al. Sheep CD34+ amniotic fluid cells have hematopoietic potential and engraft after autologous in utero transplantation. Stem Cells. 2015; 33: 122–32.Google Scholar
Alton, EWFW, Armstrong, DK, Ashby, D, Bayfield, KJ, Bilton, D, Bloomfield, EV, 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: 684–91.Google Scholar
Griesenbach, U, Inoue, M, Meng, C, Farley, R, Chan, M, Newman, NK, et al. Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. Am J Respir Crit Care Med. 2012; 186: 846–56.Google Scholar
Alton, EWFW, Beekman, JM, Boyd, AC, Brand, J, Carlon, MS, Connolly, MM, et al. Preparation for a first-in-man lentivirus trial in patients with cystic fibrosis. Thorax. 2017; 72: 137–47.CrossRefGoogle ScholarPubMed
Larson, JE, Morrow, SL, Happel, L, Sharp, JF, Cohen, JC. Reversal of cystic fibrosis phenotype in mice by gene therapy in utero. Lancet. 1997; 349: 619–20.CrossRefGoogle ScholarPubMed
Buckley, SMK, Waddington, SN, Jezzard, S, Bergau, A, Themis, M, MacVinish, LJ, et al. Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice. Mol Ther. 2008; 16: 819–24.Google Scholar
Davies, LA, Varathalingam, A, Painter, H, Lawton, AE, Sumner-Jones, SG, Nunez-Alonso, GA, et al. Adenovirus-mediated in utero expression of CFTR does not improve survival of CFTR knockout mice. Mol Ther. 2008; 16: 812–18.CrossRefGoogle Scholar
Buckley, SMK, Howe, SJ, Sheard, V, Ward, NJ, Coutelle, C, Thrasher, AJ, et al. Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression. Gene Ther. 2008; 15: 1167–75.CrossRefGoogle ScholarPubMed
Buckley, SMK, Waddington, SN, Jezzard, S, Lawrence, L, Schneider, H, Holder, M V, et al. Factors influencing adenovirus-mediated airway transduction in fetal mice. Mol Ther. 2005; 12: 484–92.Google Scholar
Moss, IR, Scarpelli, EM. Stimulatory effect of theophylline on regulation of fetal breathing movements. Pediatr Res. 1981; 15: 870–3.CrossRefGoogle ScholarPubMed
Henriques-Coelho, T, Gonzaga, S, Endo, M, Zoltick, PW, Davey, M, Leite-Moreira, AF, et al. Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided intrapulmonary injection. Mol Ther. 2007; 15: 340–7.Google Scholar
Toelen, J, Deroose, CM, Gijsbers, R, Reumers, V, Sbragia, LN, Vets, S, et al. Fetal gene transfer with lentiviral vectors: long-term in vivo follow-up evaluation in a rat model. Am J Obstet Gynecol. 2007; 196. 352. e1–6.CrossRefGoogle ScholarPubMed
Tarantal, AF, Lee, CI, Ekert, JE, McDonald, R, Kohn, DB, Plopper, CG, et al. Lentiviral vector gene transfer into fetal rhesus monkeys (Macaca mulatta): lung-targeting approaches. Mol Ther. 2001; 4: 614–21.Google Scholar
Tarantal, AF, McDonald, RJ, Jimenez, DF, Lee, CCI, O’Shea, CE, Leapley, AC, et al. Intrapulmonary and intramyocardial gene transfer in rhesus monkeys (Macaca mulatta): safety and efficiency of HIV-1-derived lentiviral vectors for fetal gene delivery. Mol Ther. 2005; 12: 87–98.CrossRefGoogle ScholarPubMed
David, AL, Peebles, DM, Gregory, L, Themis, M, Cook, T, Coutelle, C, et al. Percutaneous ultrasound-guided injection of the trachea in fetal sheep: A novel technique to target the fetal airways. Fetal Diagn Ther. 2003; 18: 385–90.Google Scholar
Peebles, D, Gregory, LG, David, A, Themis, M, Waddington, SN, Knapton, HJ, et al. Widespread and efficient marker gene expression in the airway epithelia of fetal sheep after minimally invasive tracheal application of recombinant adenovirus in utero. Gene Ther. 2004; 11: 70–8.CrossRefGoogle ScholarPubMed
Gregory, LG, Harbottle, RP, Lawrence, L, Knapton, HJ, Themis, M, Coutelle, C. Enhancement of adenovirus-mediated gene transfer to the airways by DEAE dextran and sodium caprate in vivo. Mol Ther. 2003; 7: 19–26.CrossRefGoogle Scholar
David, AL, Peebles, DM, Gregory, L, Waddington, SN, Themis, M, Weisz, B, et al. Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: toward prenatal prevention of early-onset intestinal diseases. Hum Gene Ther. 2006; 17 : 767–79.CrossRefGoogle ScholarPubMed
Saada, J, Oudrhiri, N, Bonnard, A, de Lagausie, P, Aissaoui, A, Hauchecorne, M, et al. Combining keratinocyte growth factor transfection into the airways and tracheal occlusion in a fetal sheep model of congenital diaphragmatic hernia. J Gene Med. 2010; 12: 413–22.CrossRefGoogle Scholar
Berges, BK, Yellayi, S, Karolewski, BA, Miselis, RR, Wolfe, JH, Fraser, NW. Widespread correction of lysosomal storage in the mucopolysaccharidosis type VII mouse brain with a herpes simplex virus type I vector expressing beta-glucuronidase. Mol Ther. 2006; 13: 859–69.Google Scholar
Ciron, C, Desmaris, N, Colle, MA, Raoul, S, Joussemet, B, Vérot, L, et al. Gene therapy of the brain in the dog model of Hurler’s syndrome. Ann Neurol. 2006; 60: 204–13.Google Scholar
Shen, JS, Meng, XL, Yokoo, T, Sakurai, K, Watabe, K, Ohashi, T, et al. Widespread and highly persistent gene transfer to the CNS by retrovirus vector in utero: implication for gene therapy to Krabbe disease. J Gene Med. 2005; 7: 540–51.Google Scholar
Karolewski, BA, Wolfe, JH. Genetic correction of the fetal brain increases the lifespan of mice with the severe multisystemic disease mucopolysaccharidosis type VII. Mol Ther. 2006; 14: 14–24.Google Scholar
Tarantal, AF, Chu, F, O’Brien, WD, Hendrickx, AG. Sonographic heat generation in vivo in the gravid long-tailed macaque (Macaca fascicularis). J Ultrasound Med. 1993; 12: 285–95.Google Scholar
Massaro, G, Mattar, CNZ, Wong, AMS, Sirka, E, Buckley, SMK, Herbert, BR, et al. Fetal gene therapy for neurodegenerative disease of infants. Nat Med. 2018; 24: 1317–23.Google Scholar
Mendell, JR, Al-Zaidy, S, Shell, R, Arnold, WD, Rodino-Klapac, LR, Prior, TW, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017; 377: 1713–22.Google Scholar
Foust, KD, Nurre, E, Montgomery, CL, Hernandez, A, Chan, CM, Kaspar, BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009; 27: 59–65.Google Scholar
Duque, S, Joussemet, B, Riviere, C, Marais, T, Dubreil, L, Douar, A-M, et al. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther. 2009; 17: 1187–96.Google Scholar
Manfredsson, FP, Rising, AC, Mandel, RJ. AAV9: A potential blood-brain barrier buster. Mol Ther. 2009; 17: 403–5.Google Scholar
Rahim, AA, Wong, AMS, Hoefer, K, Buckley, SMK, Mattar, CN, Cheng, SH, et al. Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system. FASEB J. 2011; 25: 3505–18.Google Scholar
Le Guiner, C, Servais, L, Montus, M, Larcher, T, Fraysse, B, Moullec, S, et al. Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy. Nat Commun. 2017; 8: 16105.CrossRefGoogle Scholar
MacKenzie, TC, Kobinger, GP, Louboutin, JP, Radu, A, Javazon, EH, Sena-Esteves, M, et al. Transduction of satellite cells after prenatal intramuscular administration of lentiviral vectors. J Gene Med. 2005; 7: 50–8.Google Scholar
Reay, DP, Bilbao, R, Koppanati, BM, Cai, L, O’Day, TL, Jiang, Z, et al. Full-length dystrophin gene transfer to the mdx mouse in utero. Gene Ther. 2008; 15: 531–6.Google Scholar
Gregory, LG, Waddington, SN, Holder, MV, Mitrophanous, KA, Buckley, SMK, Mosley, KL, et al. Highly efficient EIAV-mediated in utero gene transfer and expression in the major muscle groups affected by Duchenne muscular dystrophy. Gene Ther. 2004; 11: 1117–25.Google Scholar
Koppanati, BM, Li, J, Reay, DP, Wang, B, Daood, M, Zheng, H, et al. Improvement of the mdx mouse dystrophic phenotype by systemic in utero AAV8 delivery of a minidystrophin gene. Gene Ther. 2010; 17: 1355–62.Google Scholar
Weisz, B, David, AL, Gregory, LG, Perocheau, D, Ruthe, A, Waddington, SN, et al. Targeting the respiratory muscles of fetal sheep for prenatal gene therapy for Duchenne muscular dystrophy. Am J Obstet Gynecol. 2005; 193: 1105–9.Google Scholar
Mühle, C, Neuner, A, Park, J, Pacho, F, Jiang, Q, Waddington, SN, et al. Evaluation of prenatal intra-amniotic LAMB3 gene delivery in a mouse model of Herlitz disease. Gene Ther. 2006; 13: 1665–76.CrossRefGoogle Scholar
Sato, M, Tanigawa, M, Kikuchi, N. Nonviral gene transfer to surface skin of mid-gestational murine embryos by intraamniotic injection and subsequent electroporation. Mol Reprod Dev. 2004; 69: 268–77.Google Scholar
Endoh, M, Koibuchi, N, Sato, M, Morishita, R, Kanzaki, T, Murata, Y, et al. Fetal gene transfer by intrauterine injection with microbubble-enhanced ultrasound. Mol Ther. 2002; 5: 501–8.Google Scholar
Yoshizawa, J, Li, XK, Fujino, M, Kimura, H, Mizuno, R, Hara, A, et al. Successful in utero gene transfer using a gene gun in midgestational mouse fetuses. J Pediatr Surg. 2004; 39: 81–4.Google Scholar
Endo, M, Zoltick, PW, Peranteau, WH, Radu, A, Muvarak, N, Ito, M, et al. Efficient in vivo targeting of epidermal stem cells by early gestational intraamniotic injection of lentiviral vector driven by the keratin 5 promoter. Mol Ther. 2008; 16: 131–7.CrossRefGoogle ScholarPubMed
Endo, M, Zoltick, PW, Radu, A, Qiujie, J, Matsui, C, Marinkovich, PM, et al. Early intra-amniotic gene transfer using lentiviral vector improves skin blistering phenotype in a murine model of Herlitz junctional epidermolysis bullosa. Gene Ther. 2012; 19: 561–9.Google Scholar
Schneider, H, Mallepell, SS, Körber, I, Wohlfart, S, Dick, A, Wahlbuhl, M, et al. Prenatal correction of X-linked hypohidrotic ectodermal dysplasia. N Engl J Med. 2018; 378: 1604–10.Google Scholar
Suff, N, Karda, R, Bajaj-Elliott, M, Buckley, SMK, Tangney, M, Waddington, SN, et al. Cervical gene delivery of human beta-defensin-3(HBD-3) prevents ascending bacterial infection in pregnant mice. Reprod Sci. 2017; 24 (Suppl. 1): 55A.Google Scholar
Miller, SL, Loose, JM, Jenkin, G, Wallace, EM. The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus. Am J Obstet Gynecol. 2009; 200: 102. e1–7.Google Scholar
David, AL, Torondel, B, Zachary, I, Wigley, V, Nader, KA, Mehta, V, et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Ther. 2008; 15: 1344–50.Google Scholar
Mehta, V, Abi-Nader, KN, Peebles, DM, Benjamin, E, Wigley, V, Torondel, B, et al. Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A165 in the uterine arteries of pregnant sheep. Gene Ther. 2012; 19: 925–35.Google Scholar
Mehta, V, Abi-Nader, KN, Shangaris, P, Shaw, SWS, Filippi, E, Benjamin, E, et al. Local over-expression of VEGF-DΔNΔC in the uterine arteries of pregnant sheep results in long-term changes in uterine artery contractility and angiogenesis. PLoS One. 2014; 9: e100021.Google Scholar
Carr, DJ, Wallace, JM, Aitken, RP, Milne, JS, Mehta, V, Martin, JF, et al. Uteroplacental adenovirus vascular endothelial growth factor gene therapy increases fetal growth velocity in growth-restricted sheep pregnancies. Hum Gene Ther. 2014; 25: 375–84.Google Scholar
Carr, DJ, Wallace, JM, Aitken, RP, Milne, JS, Martin, JF, Zachary, IC, et al. Peri- and postnatal effects of prenatal adenoviral VEGF gene therapy in growth-restricted sheep. Biol Reprod. 2016; 94: 142.Google Scholar
Swanson, AM, Rossi, CA, Ofir, K, Mehta, V, Boyd, M, Barker, H, et al. Maternal therapy with Ad.VEGF-A165 increases fetal weight at term in a guinea pig model of fetal growth restriction. Hum Gene Ther. 2016; 27: 997–1007.Google Scholar
Vaughan, OR, Rossi, CA, Ginsberg, Y, White, A, Hristova, M, Sebire, NJ, et al. Perinatal and long term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth restricted guinea pig fetus. Am J Physiol Regul Integr Comp Physiol. 2018; 315: R344–53.Google Scholar
Gancberg, D, Hoeveler, A, Draghia-Akli, R. Gene therapy and gene transfer projects of the 7th Framework Programme for Research and Technological Development of the European Union. Hum Gene Ther Clin Dev. 2015; 26: 77.Google Scholar
Guo, ZS, Li, Q, Bartlett, DL, Yang, JY, Fang, B. Gene transfer: the challenge of regulated gene expression. Trends Mol Med. 2008; 14: 410–18.Google Scholar
Coutelle, C, Waddington, SN. Vector systems for prenatal gene therapy: choosing vectors for different Applications. In Prenatal Gene Therapy. Totowa, NJ: Humana Press, 2012, pp. 41–53.Google Scholar
Merten, OW, Hebben, M, Bovolenta, C. Production of lentiviral vectors. Mol Ther Methods Clin Dev. 2016; 3: 16017.Google Scholar
Manceur, AP, Kim, H, Misic, V, Andreev, N, Dorion-Thibaudeau, J, Lanthier, S, et al. Scalable lentiviral vector production using stable HEK293SF producer cell lines. Hum Gene Ther Methods. 2017; 28: 330–9.Google Scholar
Douar, AM, Themis, M, Sandig, V, Friedmann, T, Coutelle, C. Effect of amniotic fluid on cationic lipid mediated transfection and retroviral infection. Gene Ther. 1996; 3: 789–96.Google Scholar
Engelstädter, M, Buchholz, CJ, Bobkova, M, Steidl, S, Merget-Millitzer, H, Willemsen, RA, et al. Targeted gene transfer to lymphocytes using murine leukaemia virus vectors pseudotyped with spleen necrosis virus envelope proteins. Gene Ther. 2001; 8: 1202–6.CrossRefGoogle ScholarPubMed
Challita, P-M, Kohn, DB. Lack of expression from a retroviral vector after transduction of murine hematopoietic stem cells is associated with methylation in vivo. Proc Natl Acad Sci USA. 1994; 91: 2567–71.Google Scholar
Jinek, M, Chylinski, K, Fonfara, I, Hauer, M, Doudna, JA, Charpentier, E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science . 2012; 337: 816–21.Google Scholar
Cong, L, Ran, FA, Cox, D, Lin, S, Barretto, R, Habib, N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013; 339: 819–23.Google Scholar
Fu, Y, Sander, JD, Reyon, D, Cascio, VM, Joung, JK. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014; 32: 279–84.Google Scholar
Slaymaker, IM, Gao, L, Zetsche, B, Scott, DA, Yan, WX, Zhang, F. Rationally engineered Cas9 nucleases with improved specificity. Science. 2016; 351: 84–8.Google Scholar
Kleinstiver, BP, Pattanayak, V, Prew, MS, Tsai, SQ, Nguyen, NT, Zheng, Z, et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016; 529: 490–5.CrossRefGoogle ScholarPubMed
Ran, FA, Cong, L, Yan, WX, Scott, DA, Gootenberg, JS, Kriz, AJ, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015; 520: 186–91.Google Scholar
Liang, P, Xu, Y, Zhang, X, Ding, C, Huang, R, Zhang, Z, et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell. 2015; 6: 363–72.Google Scholar
Fogarty, NME, McCarthy, A, Snijders, KE, Powell, BE, Kubikova, N, Blakeley, P, et al. Genome editing reveals a role for OCT4 in human embryogenesis. Nature. 2017; 550: 67–73.Google Scholar
Ma, H, Marti-Gutierrez, N, Park, S-W, Wu, J, Lee, Y, Suzuki, K, et al. Correction of a pathogenic gene mutation in human embryos. Nature. 2017; 548: 413–19.CrossRefGoogle ScholarPubMed
Suzuki, T, Asami, M, Perry, ACF. Asymmetric parental genome engineering by Cas9 during mouse meiotic exit. Sci Rep. 2014; 4: 7621.CrossRefGoogle ScholarPubMed
David, AL, Weisz, B, Gregory, L, Themis, M, Cook, T, Roubliova, X, et al. Ultrasound-guided injection and occlusion of the trachea in fetal sheep. Ultrasound Obstet Gynecol. 2006; 28: 82–8.CrossRefGoogle ScholarPubMed
Jiménez, JA, Eixarch, E, DeKoninck, P, Bennini, JR, Devlieger, R, Peralta, CF, et al. Balloon removal after fetoscopic endoluminal tracheal occlusion for congenital diaphragmatic hernia. Am J Obstet Gynecol. 2017; 217: 78. e1–78. e11.CrossRefGoogle ScholarPubMed
Coutelle, C, Themis, M, Waddington, SN, Buckley, SMK, Gregory, LG, Nivsarkar, MS, et al. Gene therapy progress and prospects: fetal gene therapy – first proofs of concept – some adverse effects. Gene Ther. 2005; 12: 1601–7.CrossRefGoogle ScholarPubMed
Huard, J, Lochmuller, H, Acsadi, G, Jani, A, Holland, P, Guerin, C, et al. Differential short-term transduction efficiency of adult versus newborn mouse tissues by adenoviral recombinants. Exp Mol Pathol. 1995; 62: 131–43.Google Scholar
Endo, M, Henriques-Coelho, T, Zoltick, PW, Stitelman, DH, Peranteau, WH, Radu, A, et al. The developmental stage determines the distribution and duration of gene expression after early intra-amniotic gene transfer using lentiviral vectors. Gene Ther. 2010; 17: 61–71.Google Scholar
Brown, BD, Gentner, B, Cantore, A, Colleoni, S, Amendola, M, Zingale, A, et al. Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol. 2007; 25: 1457–67.Google Scholar
Shaw, SWS, David, AL, De Coppi, P. Clinical applications of prenatal and postnatal therapy using stem cells retrieved from amniotic fluid. Curr Opin Obstet Gynecol. 2011; 23: 109–16.Google Scholar
Steven Shaw, SW, Bollini, S, Nader, KA, Gastadello, A, Mehta, V, Filppi, E, et al. Autologous transplantation of amniotic fluid-derived mesenchymal stem cells into sheep fetuses. Cell Transplant. 2011; 20: 1015–31.Google Scholar
Shaw, SWS, Blundell, MP, Pipino, C, Shangaris, P, Maghsoudlou, P, Ramachandra, DL, et al. Sheep CD34+ amniotic fluid cells have hematopoietic potential and engraft after autologous in utero transplantation. Stem Cells. 2015; 33: 122–32.Google Scholar
Ellis, J. Silencing and variegation of gammaretrovirus and lentivirus vectors. Hum Gene Ther. 2005; 16: 1241–6.Google Scholar
Jerebtsova, M, Batshaw, ML, Ye, X. Humoral immune response to recombinant adenovirus and adeno-associated virus after in utero administration of viral vectors in mice. Pediatr Res. 2002; 52: 95–104.Google Scholar
Seppen, J, van Til, NP, van der Rijt, R, Hiralall, JK, Kunne, C, Oude Elferink, RPJ. Immune response to lentiviral bilirubin UDP-glucuronosyltransferase gene transfer in fetal and neonatal rats. Gene Ther. 2006; 13: 672–7.Google Scholar
Manno, CS, Pierce, GF, Arruda, VR, Glader, B, Ragni, M, Rasko, JJ, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006; 12: 342–7.Google Scholar
Wenstrom, KD, Andrews, WW, Bowles, NE, Towbin, JA, Hauth, JC, Goldenberg, RL. Intrauterine viral infection at the time of second trimester genetic amniocentesis. Obstet Gynecol. 1998; 92: 420–4.Google Scholar
Porada, CD, Park, PJ, Tellez, J, Ozturk, F, Glimp, HA, Almeida-Porada, G, et al. Male germ-line cells are at risk following direct-injection retroviral-mediated gene transfer in utero. Mol Ther. 2005; 12: 754–62.Google Scholar
Heikkilä, A, Hiltunen, MO, Turunen, MP, Keski-Nisula, L, Turunen, A-M, Räsänen, H, et al. Angiographically guided utero-placental gene transfer in rabbits with adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine complexes. Gene Ther. 2001; 8: 784–8.Google Scholar
MacCalman, CD, Furth, EE, Omigbodun, A, Kozarsky, KF, Coutifaris, C, Strauss, JF. Transduction of human trophoblast cells by recombinant adenoviruses is differentiation dependent. Biol Reprod. 1996; 54: 682–91.Google Scholar
Desforges, M, Rogue, A, Pearson, N, Rossi, C, Olearo, E, Forster, R, et al. In vitro human placental studies to support adenovirus-mediated VEGF-DΔNΔC maternal gene therapy for the treatment of severe early-onset fetal growth restriction. Hum Gene Ther Clin Dev. 2018; 29: 10–23.CrossRefGoogle Scholar
Koi, H, Zhang, J, Makrigiannakis, A, Getsios, S, MacCalman, CD, Kopf, GS, et al. Differential expression of the coxsackievirus and adenovirus receptor regulates adenovirus infection of the placenta. Biol Reprod. 2001; 64: 1001–9.Google Scholar
Raper, SE, Chirmule, N, Lee, FS, Wivel, NA, Bagg, A, Gao, GP, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab. 2003; 80: 148–58.Google Scholar
Bedrosian, JC, Gratton, MA, Brigande, JV, Tang, W, Landau, J, Bennett, J. In vivo delivery of recombinant viruses to the fetal murine cochlea: transduction characteristics and long-term effects on auditory function. Mol Ther. 2006; 14: 328–35.Google Scholar
Hacein-Bey-Abina, S, Pai, S-Y, Gaspar, HB, Armant, M, Berry, CC, Blanche, S, et al. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med. 2014; 371: 1407–17.Google Scholar
David, RM, Doherty, AT. Viral Vectors: The road to reducing genotoxicity. Toxicol Sci. 2017; 155: 315–25.Google Scholar
Themis, M, Waddington, SN, Schmidt, M, von Kalle, C, Wang, Y, Al-Allaf, F, et al. Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice. Mol Ther. 2005; 12: 763–71.Google Scholar
Chandler, RJ, LaFave, MC, Varshney, GK, Trivedi, NS, Carrillo-Carrasco, N, Senac, JS, et al. Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J Clin Invest. 2015; 125: 870–80.Google Scholar
Morrow, SL, Larson, JE, Nelson, S, Sekhon, HS, Ren, T, Cohen, JC. Modification of development by the CFTR gene in utero. Mol Genet Metab. 1998; 65: 203–12.CrossRefGoogle ScholarPubMed
Larson, JE, Delcarpio, JB, Farberman, MM, Morrow, SL, Cohen, JC. CFTR modulates lung secretory cell proliferation and differentiation. Am J Physiol Lung Cell Mol Physiol. 2000; 279: L333–41.Google Scholar
Gonzaga, S, Henriques-Coelho, T, Davey, M, Zoltick, PW, Leite-Moreira, AF, Correia-Pinto, J, et al. Cystic adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung. Am J Respir Cell Mol Biol. 2008; 39: 346–55.Google Scholar
Tarantal, AF, Chen, H, Shi, TT, Lu, CH, Fang, AB, Buckley, S, et al. Overexpression of transforming growth factor-β1 in fetal monkey lung results in prenatal pulmonary fibrosis. Eur Respir J. 2010; 36: 907–14.Google Scholar
Pahal, GS, Jauniaux, E, Kinnon, C, Thrasher, AJ, Rodeck, CH. Normal development of human fetal hematopoiesis between eight and seventeen weeks’ gestation. Am J Obstet Gynecol. 2000; 183: 1029–34.Google Scholar
Sheppard, M, Spencer, RN, Ashcroft, R, David, AL. Ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early-onset fetal growth restriction. Ultrasound Obstet Gynecol. 2016; 47: 484–91.Google Scholar
European Medicines Agency. (2018). Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-quality-non-clinical-clinical-aspects-gene-therapy-medicinal-products_en.pdfGoogle Scholar

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