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Open Access 01-12-2017 | Review

Genome editing for inborn errors of metabolism: advancing towards the clinic

Authors: Jessica L. Schneller, Ciaran M. Lee, Gang Bao, Charles P. Venditti

Published in: BMC Medicine | Issue 1/2017

Abstract

Inborn errors of metabolism (IEM) include many disorders for which current treatments aim to ameliorate disease manifestations, but are not curative. Advances in the field of genome editing have recently resulted in the in vivo correction of murine models of IEM. Site-specific endonucleases, such as zinc-finger nucleases and the CRISPR/Cas9 system, in combination with delivery vectors engineered to target disease tissue, have enabled correction of mutations in disease models of hemophilia B, hereditary tyrosinemia type I, ornithine transcarbamylase deficiency, and lysosomal storage disorders. These in vivo gene correction studies, as well as an overview of genome editing and future directions for the field, are reviewed and discussed herein.

Lanpher B, Brunetti-Pierri N, Lee B. Inborn errors of metabolism: the flux from Mendelian to complex diseases. Nat Rev Genet. 2006;7(6):449–60.CrossRefPubMed

Lee B, Rhead W, Diaz GA, Scharschmidt BF, Mian A, Shchelochkov O, Marier JF, Beliveau M, Mauney J, Dickinson K, et al. Phase 2 comparison of a novel ammonia scavenging agent with sodium phenylbutyrate in patients with urea cycle disorders: safety, pharmacokinetics and ammonia control. Mol Genet Metab. 2010;100(3):221–8.CrossRefPubMedPubMedCentral

Brunetti-Pierri N, Lee B. Gene therapy for inborn errors of liver metabolism. Mol Genet Metab. 2005;86(1-2):13–24.CrossRefPubMed

Cunningham SC, Kok CY, Dane AP, Carpenter K, Kizana E, Kuchel PW, Alexander IE. Induction and prevention of severe hyperammonemia in the spfash mouse model of ornithine transcarbamylase deficiency using shRNA and rAAV-mediated gene delivery. Mol Ther. 2011;19(5):854–9.CrossRefPubMedPubMedCentral

Foschi FG, Morelli MC, Savini S, Dall’Aglio AC, Lanzi A, Cescon M, Ercolani G, Cucchetti A, Pinna AD, Stefanini GF. Urea cycle disorders: a case report of a successful treatment with liver transplant and a literature review. World J Gastroenterol. 2015;21(13):4063–8.CrossRefPubMedPubMedCentral

Sloan JL, Manoli I, Venditti CP. Liver or combined liver-kidney transplantation for patients with isolated methylmalonic acidemia: who and when? J Pediatr. 2015;166(6):1346–50.CrossRefPubMed

Mc Guire PJ, Lim-Melia E, Diaz GA, Raymond K, Larkin A, Wasserstein MP, Sansaricq C. Combined liver-kidney transplant for the management of methylmalonic aciduria: a case report and review of the literature. Mol Genet Metab. 2008;93(1):22–9.CrossRefPubMed

Corti M, Elder M, Falk D, Lawson L, Smith B, Nayak S, Conlon T, Clement N, Erger K, Lavassani E, et al. B-Cell Depletion is Protective Against Anti-AAV Capsid Immune Response: A Human Subject Case Study. Mol Ther Methods Clin Dev. 2014;1.

Kotin RM, Linden RM, Berns KI. Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J. 1992;11(13):5071–8.PubMedPubMedCentral

10.

Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci U S A. 2002;99(18):11854–9.CrossRefPubMedPubMedCentral

11.

Cunningham SC, Dane AP, Spinoulas A, Logan GJ, Alexander IE. Gene delivery to the juvenile mouse liver using AAV2/8 vectors. Mol Ther. 2008;16(6):1081–8.CrossRef

12.

Cecchini S, Virag T, Kotin RM. Reproducible high yields of recombinant adeno-associated virus produced using invertebrate cells in 0.02- to 200-liter cultures. Hum Gene Ther. 2011;22(8):1021–30.CrossRefPubMedPubMedCentral

13.

Donsante A, Miller DG, Li Y, Vogler C, Brunt EM, Russell DW, Sands MS. AAV vector integration sites in mouse hepatocellular carcinoma. Science. 2007;317(5837):477.CrossRefPubMed

14.

Chandler RJ, LaFave MC, Varshney GK, Trivedi NS, Carrillo-Carrasco N, Senac JS, Wu W, Hoffmann V, Elkahloun AG, Burgess SM, et al. Vector design influences hepatic genotoxicity after adeno-associated virus gene therapy. J Clin Invest. 2015;125(2):870–80.CrossRefPubMedPubMedCentral

15.

Nault JC, Datta S, Imbeaud S, Franconi A, Mallet M, Couchy G, Letouze E, Pilati C, Verret B, Blanc JF, et al. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas. Nat Genet. 2015;47(10):1187–93.CrossRefPubMed

16.

Rouet P, Smih F, Jasin M. Introduction of double-strand breaks into the genome of mouse cells by expression of a rare-cutting endonuclease. Mol Cell Biol. 1994;14(12):8096–106.CrossRefPubMedPubMedCentral

17.

Rouet P, Smih F, Jasin M. Expression of a site-specific endonuclease stimulates homologous recombination in mammalian cells. Proc Natl Acad Sci U S A. 1994;91(13):6064–8.CrossRefPubMedPubMedCentral

18.

Porteus MH, Baltimore D. Chimeric nucleases stimulate gene targeting in human cells. Science. 2003;300(5620):763.CrossRefPubMed

19.

Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, Jamieson AC, Porteus MH, Gregory PD, Holmes MC. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature. 2005;435(7042):646–51.CrossRefPubMed

20.

Bibikova M, Golic M, Golic KG, Carroll D. Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics. 2002;161(3):1169–75.PubMedPubMedCentral

21.

Kim YG, Cha J, Chandrasegaran S. Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci U S A. 1996;93(3):1156–60.CrossRefPubMedPubMedCentral

22.

Smith J, Bibikova M, Whitby FG, Reddy AR, Chandrasegaran S, Carroll D. Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res. 2000;28(17):3361–9.CrossRefPubMedPubMedCentral

23.

Joung JK, Sander JD. TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol. 2013;14(1):49–55.CrossRefPubMed

24.

Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. CRISPR provides acquired resistance against viruses in prokaryotes. Science. 2007;315(5819):1709–12.CrossRefPubMed

25.

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(6096):816–21.CrossRefPubMed

26.

Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, Hsu PD, Wu X, Jiang W, Marraffini LA, et al. Multiplex genome engineering using CRISPR/Cas systems. Science. 2013;339(6121):819–23.CrossRefPubMedPubMedCentral

27.

Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM. RNA-guided human genome engineering via Cas9. Science. 2013;339(6121):823–6.CrossRefPubMedPubMedCentral

28.

Lin HF, Maeda N, Smithies O, Straight DL, Stafford DW. A coagulation factor IX-deficient mouse model for human hemophilia B. Blood. 1997;90(10):3962–6.PubMed

29.

Aponte JL, Sega GA, Hauser LJ, Dhar MS, Withrow CM, Carpenter DA, Rinchik EM, Culiat CT, Johnson DK. Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1. Proc Natl Acad Sci U S A. 2001;98(2):641–5.CrossRefPubMedPubMedCentral

30.

Hodges PE, Rosenberg LE. The spfash mouse: a missense mutation in the ornithine transcarbamylase gene also causes aberrant mRNA splicing. Proc Natl Acad Sci U S A. 1989;86(11):4142–6.CrossRefPubMedPubMedCentral

31.

Li H, Haurigot V, Doyon Y, Li T, Wong SY, Bhagwat AS, Malani N, Anguela XM, Sharma R, Ivanciu L, et al. In vivo genome editing restores haemostasis in a mouse model of haemophilia. Nature. 2011;475(7355):217–21.CrossRefPubMedPubMedCentral

32.

George LA, Fogarty PF. Gene therapy for hemophilia: past, present and future. Semin Hematol. 2016;53(1):46–54.CrossRefPubMed

33.

Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187–97.CrossRefPubMed

34.

Sharma R, Anguela XM, Doyon Y, Wechsler T, DeKelver RC, Sproul S, Paschon DE, Miller JC, Davidson RJ, Shivak D, et al. In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood. 2015;126(15):1777–84.CrossRefPubMedPubMedCentral

35.

Barzel A, Paulk NK, Shi Y, Huang Y, Chu K, Zhang F, Valdmanis PN, Spector LP, Porteus MH, Gaensler KM, et al. Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature. 2015;517(7534):360–4.CrossRefPubMed

36.

Azuma H, Paulk N, Ranade A, Dorrell C, Al-Dhalimy M, Ellis E, Strom S, Kay MA, Finegold M, Grompe M. Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice. Nat Biotechnol. 2007;25(8):903–10.CrossRefPubMedPubMedCentral

37.

Yin H, Xue W, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T, Anderson DG. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol. 2014;32(6):551–3.CrossRefPubMedPubMedCentral

38.

Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q, Park A, Yang J, Suresh S, Bizhanova A, et al. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol. 2016;34(3):328–33.CrossRefPubMed

39.

Endo F, Kubo S, Awata H, Kiwaki K, Katoh H, Kanegae Y, Saito I, Miyazaki J, Yamamoto T, Jakobs C, et al. Complete rescue of lethal albino c14CoS mice by null mutation of 4-hydroxyphenylpyruvate dioxygenase and induction of apoptosis of hepatocytes in these mice by in vivo retrieval of the tyrosine catabolic pathway. J Biol Chem. 1997;272(39):24426–32.CrossRefPubMed

40.

Pankowicz FP, Barzi M, Legras X, Hubert L, Mi T, Tomolonis JA, Ravishankar M, Sun Q, Yang D, Borowiak M, et al. Reprogramming metabolic pathways in vivo with CRISPR/Cas9 genome editing to treat hereditary tyrosinaemia. Nat Commun. 2016;7:12642.CrossRefPubMedPubMedCentral

41.

Paulk NK, Wursthorn K, Haft A, Pelz C, Clarke G, Newell AH, Olson SB, Harding CO, Finegold MJ, Bateman RL, et al. In vivo selection of transplanted hepatocytes by pharmacological inhibition of fumarylacetoacetate hydrolase in wild-type mice. Mol Ther. 2012;20(10):1981–7.CrossRefPubMedPubMedCentral

42.

Nygaard S, Barzel A, Haft A, Major A, Finegold M, Kay MA, Grompe M. A universal system to select gene-modified hepatocytes in vivo. Sci Transl Med. 2016;8(342):342ra379.CrossRef

43.

Alexander IE, Cunningham SC, Logan GJ, Christodoulou J. Potential of AAV vectors in the treatment of metabolic disease. Gene Ther. 2008;15(11):831–9.CrossRefPubMed

44.

Yang Y, Wang L, Bell P, McMenamin D, He Z, White J, Yu H, Xu C, Morizono H, Musunuru K, et al. A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol. 2016;34(3):334–8.CrossRefPubMedPubMedCentral

45.

Landau DJ, Brooks ED, Perez-Pinera P, Amarasekara H, Mefferd A, Li S, Bird A, Gersbach CA, Koeberl DD. In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA. Mol Ther. 2016;24(4):697–706.CrossRefPubMed

46.

Wang J, Exline CM, DeClercq JJ, Llewellyn GN, Hayward SB, Li PW, Shivak DA, Surosky RT, Gregory PD, Holmes MC, et al. Homology-driven genome editing in hematopoietic stem and progenitor cells using ZFN mRNA and AAV6 donors. Nat Biotechnol. 2015;33(12):1256–63.CrossRefPubMedPubMedCentral

47.

Wang J, DeClercq JJ, Hayward SB, Li PW, Shivak DA, Gregory PD, Lee G, Holmes MC. Highly efficient homology-driven genome editing in human T cells by combining zinc-finger nuclease mRNA and AAV6 donor delivery. Nucleic Acids Res. 2016;44(3):e30.CrossRefPubMed

48.

DeKelver RC, Choi VM, Moehle EA, Paschon DE, Hockemeyer D, Meijsing SH, Sancak Y, Cui X, Steine EJ, Miller JC, et al. Functional genomics, proteomics, and regulatory DNA analysis in isogenic settings using zinc finger nuclease-driven transgenesis into a safe harbor locus in the human genome. Genome Res. 2010;20(8):1133–42.CrossRefPubMedPubMedCentral

49.

Rizzuto G, Gorgoni B, Cappelletti M, Lazzaro D, Gloaguen I, Poli V, Sgura A, Cimini D, Ciliberto G, Cortese R, et al. Development of animal models for adeno-associated virus site-specific integration. J Virol. 1999;73(3):2517–26.PubMedPubMedCentral

50.

Gasiunas G, Barrangou R, Horvath P, Siksnys V. Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci U S A. 2012;109(39):E2579–2586.CrossRefPubMedPubMedCentral

51.

Esvelt KM, Mali P, Braff JL, Moosburner M, Yaung SJ, Church GM. Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nat Methods. 2013;10(11):1116–21.CrossRefPubMedPubMedCentral

52.

Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520(7546):186–91.CrossRefPubMedPubMedCentral

53.

Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS, Essletzbichler P, Volz SE, Joung J, van der Oost J, Regev A, et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell. 2015;163(3):759–71.CrossRefPubMedPubMedCentral

54.

Kleinstiver BP, Tsai SQ, Prew MS, Nguyen NT, Welch MM, Lopez JM, McCaw ZR, Aryee MJ, Joung JK. Genome-wide specificities of CRISPR-Cas Cpf1 nucleases in human cells. Nat Biotechnol. 2016;34(8):869–74.CrossRefPubMedPubMedCentral

55.

Kim D, Kim J, Hur JK, Been KW, Yoon SH, Kim JS. Genome-wide analysis reveals specificities of Cpf1 endonucleases in human cells. Nat Biotechnol. 2016;34(8):863–8.CrossRefPubMed

56.

Abudayyeh OO, Gootenberg JS, Konermann S, Joung J, Slaymaker IM, Cox DB, Shmakov S, Makarova KS, Semenova E, Minakhin L, et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science. 2016;353(6299):aaf5573.CrossRefPubMedPubMedCentral

57.

Kleinstiver BP, Prew MS, Tsai SQ, Nguyen NT, Topkar VV, Zheng Z, Joung JK. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat Biotechnol. 2015;33(12):1293–8.CrossRefPubMedPubMedCentral

58.

Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng Z, Gonzales AP, Li Z, Peterson RT, Yeh JR, et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015;523(7561):481–5.CrossRefPubMedPubMedCentral

59.

Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng Z, Joung JK. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529(7587):490–5.CrossRefPubMedPubMedCentral

60.

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.CrossRefPubMedPubMedCentral

61.

Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, Sur M, Zhang F. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat Biotechnol. 2015;33(1):102–6.CrossRefPubMed

62.

Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science. 1989;244(4912):1578–80.CrossRefPubMed

63.

Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Castellanos Rivera RM, Madhavan S, Pan X, Ran FA, Yan WX, et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016;351(6271):403–7.CrossRefPubMed

64.

Tabebordbar M, Zhu K, Cheng JK, Chew WL, Widrick JJ, Yan WX, Maesner C, Wu EY, Xiao R, Ran FA, et al. In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. 2016;351(6271):407–11.CrossRefPubMed

65.

Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, Bhattacharyya S, Shelton JM, Bassel-Duby R, Olson EN. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science. 2016;351(6271):400–3.CrossRefPubMed

66.

Zhang Y, Chirmule N, Gao G, Wilson J. CD40 ligand-dependent activation of cytotoxic T lymphocytes by adeno-associated virus vectors in vivo: role of immature dendritic cells. J Virol. 2000;74(17):8003–10.CrossRefPubMedPubMedCentral

67.

Zaiss AK, Liu Q, Bowen GP, Wong NC, Bartlett JS, Muruve DA. Differential activation of innate immune responses by adenovirus and adeno-associated virus vectors. J Virol. 2002;76(9):4580–90.CrossRefPubMedPubMedCentral

68.

Somanathan S, Breous E, Bell P, Wilson JM. AAV vectors avoid inflammatory signals necessary to render transduced hepatocyte targets for destructive T cells. Mol Ther. 2010;18(5):977–82.CrossRefPubMedPubMedCentral

69.

Mays LE, Wilson JM. The complex and evolving story of T cell activation to AAV vector-encoded transgene products. Mol Ther. 2011;19(1):16–27.CrossRefPubMed

70.

Chew WL, Tabebordbar M, Cheng JK, Mali P, Wu EY, Ng AH, Zhu K, Wagers AJ, Church GM. A multifunctional AAV-CRISPR-Cas9 and its host response. Nat Methods. 2016;13(10):868–74.CrossRefPubMed

71.

Cradick TJ, Qiu P, Lee CM, Fine EJ, Bao G. COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites. Mol Ther Nucleic Acids. 2014;3:e214.CrossRefPubMedPubMedCentral

72.

Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O, et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013;31(9):827–32.CrossRefPubMedPubMedCentral

73.

Haeussler M, Schonig K, Eckert H, Eschstruth A, Mianne J, Renaud JB, Schneider-Maunoury S, Shkumatava A, Teboul L, Kent J, et al. Evaluation of off-target and on-target scoring algorithms and integration into the guide RNA selection tool CRISPOR. Genome Biol. 2016;17(1):148.CrossRefPubMedPubMedCentral

74.

DeWitt MA, Magis W, Bray NL, Wang T, Berman JR, Urbinati F, Heo SJ, Mitros T, Munoz DP, Boffelli D, et al. Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells. Sci Transl Med. 2016;8((360):360ra134.CrossRefPubMed

75.

Muller M, Lee CM, Gasiunas G, Davis TH, Cradick TJ, Siksnys V, Bao G, Cathomen T, Mussolino C. Streptococcus thermophilus CRISPR-Cas9 Systems Enable Specific Editing of the Human Genome. Mol Ther. 2016;24(3):636–44.CrossRefPubMed

76.

Lee CM, Cradick TJ, Bao G. The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells. Mol Ther. 2016;24(3):645–54.CrossRefPubMedPubMedCentral

77.

Friedland AE, Baral R, Singhal P, Loveluck K, Shen S, Sanchez M, Marco E, Gotta GM, Maeder ML, Kennedy EM, et al. Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications. Genome Biol. 2015;16:257.CrossRefPubMedPubMedCentral

78.

Liu KI, Ramli MN, Woo CW, Wang Y, Zhao T, Zhang X, Yim GR, Chong BY, Gowher A, Chua MZ, et al. A chemical-inducible CRISPR-Cas9 system for rapid control of genome editing. Nat Chem Biol. 2016;12(11):980–7.CrossRefPubMed

79.

Guilinger JP, Thompson DB, Liu DR. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol. 2014;32(6):577–82.CrossRefPubMedPubMedCentral

80.

Bahal R, Ali McNeer N, Quijano E, Liu Y, Sulkowski P, Turchick A, Lu YC, Bhunia DC, Manna A, Greiner DL, et al. In vivo correction of anaemia in beta-thalassemic mice by gammaPNA-mediated gene editing with nanoparticle delivery. Nat Commun. 2016;7:13304.CrossRefPubMedPubMedCentral

81.

Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med. 2014;370(10):901–10.CrossRefPubMedPubMedCentral

Title: Genome editing for inborn errors of metabolism: advancing towards the clinic
Authors: Jessica L. Schneller
Ciaran M. Lee
Gang Bao
Charles P. Venditti
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-017-0798-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Genome editing for inborn errors of metabolism: advancing towards the clinic

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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