BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

Therapeutic applications of gene editing in chronic liver diseases: an update

  • Shin, Ji Hyun (Department of Surgery, Hanyang University College of Medicine) ;
  • Lee, Jinho (Department of Surgery, Hanyang University College of Medicine) ;
  • Jung, Yun Kyung (Department of Surgery, Hanyang University College of Medicine) ;
  • Kim, Kyeong Sik (Department of Surgery, Hanyang University College of Medicine) ;
  • Jeong, Jaemin (Department of Surgery, Hanyang University College of Medicine) ;
  • Choi, Dongho (Department of Surgery, Hanyang University College of Medicine)
  • 투고 : 2022.01.03
  • 심사 : 2022.04.22
  • 발행 : 2022.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Innovative genome editing techniques developed in recent decades have revolutionized the biomedical research field. Liver is the most favored target organ for genome editing owing to its ability to regenerate. The regenerative capacity of the liver enables ex vivo gene editing in which the mutated gene in hepatocytes isolated from the animal model of genetic disease is repaired. The edited hepatocytes are injected back into the animal to mitigate the disease. Furthermore, the liver is considered as the easiest target organ for gene editing as it absorbs almost all foreign molecules. The mRNA vaccines, which have been developed to manage the COVID-19 pandemic, have provided a novel gene editing strategy using Cas mRNA. A single injection of gene editing components with Cas mRNA is reported to be efficient in the treatment of patients with genetic liver diseases. In this review, we first discuss previously reported gene editing tools and cases managed using them, as well as liver diseases caused by genetic mutations. Next, we summarize the recent successes of ex vivo and in vivo gene editing approaches in ameliorating liver diseases in animals and humans.

키워드

과제정보

This work was supported by the research fund of Hanyang University (HY-201900000003369).

참고문헌

  1. Hackl C, Schlitt HJ, Melter M, Knoppke B and Loss M (2015) Current developments in pediatric liver transplantation. World J Hepatol 7, 1509-1520 https://doi.org/10.4254/wjh.v7.i11.1509
  2. Blaese RM, Culver KW, Miller AD et al (1995) T lymphocyte-directed gene therapy for ADA- SCID: initial trial results after 4 years. Science 270, 475-480 https://doi.org/10.1126/science.270.5235.475
  3. Kumar SR, Markusic DM, Biswas M, High KA and Herzog RW (2016) Clinical development of gene therapy: results and lessons from recent successes. Mol Ther Methods Clin Dev 3, 16034 https://doi.org/10.1038/mtm.2016.34
  4. Raper SE, Chirmule N, Lee FS et al (2003) Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 80, 148-158 https://doi.org/10.1016/j.ymgme.2003.08.016
  5. Rees HA and Liu DR (2018) Base editing: precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet 19, 770-788 https://doi.org/10.1038/s41576-018-0059-1
  6. Gaudelli NM, Komor AC, Rees HA et al (2017) Programmable base editing of A*T to G*C in genomic DNA without DNA cleavage. Nature 551, 464-471 https://doi.org/10.1038/nature24644
  7. Anzalone AV, Randolph PB, Davis JR et al (2019) Search-and-replace genome editing without double-strand breaks or donor DNA. Nature 576, 149-157 https://doi.org/10.1038/s41586-019-1711-4
  8. Anzalone AV, Koblan LW and Liu DR (2020) Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat Biotechnol 38, 824-844 https://doi.org/10.1038/s41587-020-0561-9
  9. Miranda E, Perez J, Ekeowa UI et al (2010) A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with alpha1-antitrypsin deficiency. Hepatology 52, 1078-1088 https://doi.org/10.1002/hep.23760
  10. Stoller JK, Hupertz V and Aboussouan LS et al (1993) Alpha-1 Antitrypsin Deficiency. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. 2006 Oct 27 [updated 2020 May 21]
  11. Smith C, Abalde-Atristain L, He C et al (2015) Efficient and allele-specific genome editing of disease loci in human iPSCs. Mol Ther 23, 570-577 https://doi.org/10.1038/mt.2014.226
  12. Carlson JA, Rogers BB, Sifers RN et al (1989) Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. J Clin Invest 83, 1183-1190 https://doi.org/10.1172/JCI113999
  13. Song CQ, Wang D, Jiang T et al (2018) In vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency. Hum Gene Ther 29, 853-860 https://doi.org/10.1089/hum.2017.225
  14. Bjursell M, Porritt MJ, Ericson E et al (2018) Therapeutic genome editing with CRISPR/Cas9 in a humanized mouse model ameliorates alpha1-antitrypsin deficiency phenotype. EBioMedicine 29, 104-111 https://doi.org/10.1016/j.ebiom.2018.02.015
  15. Shen S, Sanchez ME, Blomenkamp K et al (2018) Amelioration of alpha-1 antitrypsin deficiency diseases with genome editing in transgenic mice. Hum Gene Ther 29, 861-873 https://doi.org/10.1089/hum.2017.227
  16. Stephens CJ, Kashentseva E, Everett W, Kaliberova L and Curiel DT (2018) Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9. Gene Ther 25, 139-156 https://doi.org/10.1038/s41434-018-0003-1
  17. Borel F, Tang Q, Gernoux G et al (2017) Survival advantage of both human hepatocyte xenografts and genome- edited hepatocytes for treatment of alpha-1 antitrypsin deficiency. Mol Ther 25, 2477-2489 https://doi.org/10.1016/j.ymthe.2017.09.020
  18. Bagnall RD, Waseem N, Green PM and Giannelli F (2002) Recurrent inversion breaking intron 1 of the factor VIII gene is a frequent cause of severe hemophilia A. Blood 99, 168-174 https://doi.org/10.1182/blood.V99.1.168
  19. Park CY, Kim DH, Son JS et al (2015) Functional correction of large factor VIII gene chromosomal inversions in hemophilia A patient-derived iPSCs using CRISPR-Cas9. Cell Stem Cell 17, 213-220 https://doi.org/10.1016/j.stem.2015.07.001
  20. Park CY, Kim J, Kweon J et al (2014) Targeted inversion and reversion of the blood coagulation factor 8 gene in human iPS cells using TALENs. Proc Natl Acad Sci U S A 111, 9253-9258 https://doi.org/10.1073/pnas.1323941111
  21. Wu Y, Hu Z, Li Z et al (2016) In situ genetic correction of F8 intron 22 inversion in hemophilia A patient-specific iPSCs. Sci Rep 6, 18865 https://doi.org/10.1038/srep18865
  22. Park CY, Sung JJ, Cho SR, Kim J and Kim DW (2019) Universal correction of blood coagulation factor viii in patient-derived induced pluripotent stem cells using CRISPR/ Cas9. Stem Cell Reports 12, 1242-1249 https://doi.org/10.1016/j.stemcr.2019.04.016
  23. Sung JJ, Park CY, Leem JW, Cho MS and Kim DW (2019) Restoration of FVIII expression by targeted gene insertion in the FVIII locus in hemophilia A patient-derived iPSCs. Exp Mol Med 51, 1-9
  24. Sharma R, Anguela XM, Doyon Y et al (2015) In vivo genome editing of the albumin locus as a platform for protein replacement therapy. Blood 126, 1777-1784
  25. Conway A, Mendel M, Kim K et al (2019) Non-viral delivery of zinc finger nuclease mRNA enables highly efficient in vivo genome editing of multiple therapeutic gene targets. Mol Ther 27, 866-877 https://doi.org/10.1016/j.ymthe.2019.03.003
  26. Barzel A, Paulk NK, Shi Y et al (2015) Promoterless gene targeting without nucleases ameliorates haemophilia B in mice. Nature 517, 360-364 https://doi.org/10.1038/nature13864
  27. Stephens CJ, Lauron EJ, Kashentseva E, Lu ZH, Yokoyama WM and Curiel DT (2019) Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9. J Control Release 298, 128-141 https://doi.org/10.1016/j.jconrel.2019.02.009
  28. Anguela XM, Sharma R, Doyon Y et al (2013) Robust ZFN-mediated genome editing in adult hemophilic mice. Blood 122, 3283-3287 https://doi.org/10.1182/blood-2013-04-497354
  29. Lyu C, Shen J, Wang R et al (2018) Targeted genome engineering in human induced pluripotent stem cells from patients with hemophilia B using the CRISPR-Cas9 system. Stem Cell Res Ther 9, 92 https://doi.org/10.1186/s13287-018-0839-8
  30. Blau N, van Spronsen FJ and Levy HL (2010) Phenylketonuria. Lancet 376, 1417-1427 https://doi.org/10.1016/S0140-6736(10)60961-0
  31. Strisciuglio P and Concolino D (2014) New strategies for the treatment of phenylketonuria (PKU). Metabolites 4, 1007-1017 https://doi.org/10.3390/metabo4041007
  32. Blau N, Shen N and Carducci C (2014) Molecular genetics and diagnosis of phenylketonuria: state of the art. Expert Rev Mol Diagn 14, 655-671 https://doi.org/10.1586/14737159.2014.923760
  33. Pan Y, Shen N, Jung-Klawitter S et al (2016) CRISPR RNA-guided FokI nucleases repair a PAH variant in a phenylketonuria model. Sci Rep 6, 35794 https://doi.org/10.1038/srep35794
  34. McDonald JD, Bode VC, Dove WF and Shedlovsky A (1990) The use of N-ethyl-N-nitrosourea to produce mouse models for human phenylketonuria and hyperphenylalaninemia. Prog Clin Biol Res 340C, 407-413
  35. Villiger L, Grisch-Chan HM, Lindsay H et al (2018) Treatment of a metabolic liver disease by in vivo genome base editing in adult mice. Nat Med 24, 1519-1525 https://doi.org/10.1038/s41591-018-0209-1
  36. Tanzi RE, Petrukhin K, Chernov I et al (1993) The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 5, 344-350 https://doi.org/10.1038/ng1293-344
  37. Sternlieb I, Van den Hamer CJ, Morell AG, Alpert S, Gregoriadis G and Scheinberg IH (1973) Lysosomal defect of hepatic copper excretion in Wilson's disease (hepatolenticular degeneration). Gastroenterology 64, 99-105 https://doi.org/10.1016/s0016-5085(73)80096-4
  38. Murillo O, Luqui DM, Gazquez C et al (2016) Long-term metabolic correction of Wilson's disease in a murine model by gene therapy. J Hepatol 64, 419-426 https://doi.org/10.1016/j.jhep.2015.09.014
  39. Donovan K and Guzman N (2021) Ornithine Transcarbamylase Deficiency. in StatPearls, Treasure Island (FL)
  40. Hodges PE and Rosenberg LE (1989) The spfash mouse: a missense mutation in the ornithine transcarbamylase gene also causes aberrant mRNA splicing. Proc Natl Acad Sci U S A 86, 4142-4146 https://doi.org/10.1073/pnas.86.11.4142
  41. Yang Y, Wang L, Bell P et al (2016) A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol 34, 334-338 https://doi.org/10.1038/nbt.3469
  42. Lindstedt S, Holme E, Lock EA, Hjalmarson O and Strandvik B (1992) Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 340, 813-817 https://doi.org/10.1016/0140-6736(92)92685-9
  43. Azuma H, Paulk N, Ranade A et al (2007) Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice. Nat Biotechnol 25, 903-910 https://doi.org/10.1038/nbt1326
  44. Paulk NK, Wursthorn K, Wang Z, Finegold MJ, Kay MA and Grompe M (2010) Adeno-associated virus gene repair corrects a mouse model of hereditary tyrosinemia in vivo. Hepatology 51, 1200-1208 https://doi.org/10.1002/hep.23481
  45. Yin H, Xue W, Chen S et al (2014) Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol 32, 551-553 https://doi.org/10.1038/nbt.2884
  46. Yao X, Wang X, Liu J et al (2017) CRISPR/Cas9 - mediated precise targeted integration in vivo using a double cut donor with short homology arms. EBioMedicine 20, 19-26 https://doi.org/10.1016/j.ebiom.2017.05.015
  47. Shao Y, Wang L, Guo N et al (2018) Cas9-nickasemediated genome editing corrects hereditary tyrosinemia in rats. J Biol Chem 293, 6883-6892 https://doi.org/10.1074/jbc.RA117.000347
  48. Shin JH, Jung S, Ramakrishna S, Kim HH and Lee J (2018) In vivo gene correction with targeted sequence substitution through microhomology-mediated end joining. Biochem Biophys Res Commun 502, 116-122 https://doi.org/10.1016/j.bbrc.2018.05.130
  49. VanLith CJ, Guthman RM, Nicolas CT et al (2019) Ex vivo hepatocyte reprograming promotes homology-directed DNA repair to correct metabolic disease in mice after transplantation. Hepatol Commun 3, 558-573 https://doi.org/10.1002/hep4.1315
  50. VanLith C, Guthman R, Nicolas CT et al (2018) Curative ex vivo hepatocyte-directed gene editing in a mouse model of hereditary tyrosinemia type 1. Hum Gene Ther 29, 1315-1326 https://doi.org/10.1089/hum.2017.252
  51. Mangeot PE, Risson V, Fusil F et al (2019) Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins. Nat Commun 10, 45 https://doi.org/10.1038/s41467-018-07845-z
  52. Ibraheim R, Song CQ, Mir A, Amrani N, Xue W and Sontheimer EJ (2018) All-in-one adeno-associated virus delivery and genome editing by Neisseria meningitidis Cas9 in vivo. Genome Biol 19, 137 https://doi.org/10.1186/s13059-018-1515-0
  53. Rossidis AC, Stratigis JD, Chadwick AC et al (2018) In utero CRISPR-mediated therapeutic editing of metabolic genes. Nat Med 24, 1513-1518 https://doi.org/10.1038/s41591-018-0184-6
  54. Diez-Fernandez C, Rufenacht V, Gemperle C, Fingerhut R and Haberle J (2018) Mutations and common variants in the human arginase 1 (ARG1) gene: Impact on patients, diagnostics, and protein structure considerations. Hum Mutat 39, 1029-1050 https://doi.org/10.1002/humu.23545
  55. Sin YY, Price PR, Ballantyne LL and Funk CD (2017) Proof-of-concept gene editing for the murine model of inducible arginase-1 deficiency. Sci Rep 7, 2585 https://doi.org/10.1038/s41598-017-02927-2
  56. Sin YY, Ballantyne LL, Richmond CR and Funk CD (2018) Transplantation of gene-edited hepatocyte-like cells modestly improves survival of arginase-1-deficient mice. Mol Ther Nucleic Acids 10, 122-130 https://doi.org/10.1016/j.omtn.2017.11.012
  57. Kim Y, Hong SA, Yu J et al (2021) Adenine base editing and prime editing of chemically derived hepatic progenitors rescue genetic liver disease. Cell Stem Cell 28, 1614-1624 e1615 https://doi.org/10.1016/j.stem.2021.04.010
  58. Kim Y, Kang K, Lee SB et al (2019) Small molecule-mediated reprogramming of human hepatocytes into bipotent progenitor cells. J Hepatol 70, 97-107 https://doi.org/10.1016/j.jhep.2018.09.007
  59. Rothgangl T, Dennis MK, Lin PJC et al (2021) In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat Biotechnol 39, 949-957 https://doi.org/10.1038/s41587-021-00933-4
  60. Musunuru K, Chadwick AC, Mizoguchi T et al (2021) In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593, 429-434 https://doi.org/10.1038/s41586-021-03534-y
  61. Gillmore JD, Gane E, Taubel J et al (2021) CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N Engl J Med 385, 493-502 https://doi.org/10.1056/NEJMoa2107454