#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

CRISPR-Cas9 as a Tool in Cancer Therapy


Authors: P. Zatloukalová;  R. Krejčíř;  D. Valík;  B. Vojtěšek
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal: Klin Onkol 2019; 32(Supplementum 3): 13-18
Category: Review
doi: https://doi.org/10.14735/amko20193S

Summary

Background: Genome editing using CRISPR-Cas9 has become one of the basic methods of biological research over a short period of time. This recently discovered system of adaptive immunity of bacteria has been adapted to the needs of science and has become a valuable tool for DNA manipulation. Its simplicity and reliability have contributed to widespread use of the method. Genome editing refers to targeted modifications of genomic DNA with single base pair accuracy. CRISPR-Cas9 differs significantly from previous technologies in the simplicity of directing the enzyme to the target sequence. In the field of cancer research, CRISPR-Cas9 has enabled the development of a number of models for the study of carcinogenesis and drug testing. From a therapeutic point of view, CRISPR-Cas9 has been applied in the field of immunotherapy, especially in ex vivo genetic modifications of the T-cells of patients.

Aim: Currently, several clinical trials are trying to verify the therapeutic potential of CRISPR-Cas9. Based on these studies, we have summarised the strategies used in the preparation of therapeutic tools useful in cancer therapy.

Conclusion: CRISPR-Cas9 appears to be crucial in basic research, particularly in the study of the function of individual genes involved in carcinogenesis. However, it will still be necessary to optimise the efficacy, safety and specificity of CRISPR-Cas9 before it is used in clinical practice.

Keywords:

CRISPR-Cas9 – immunother­apy – clinical trial


Zdroje

1. Cong L, Ran FA, Cox D et al. Multiplex genome engineer­­ing us­­ing CRISPR/ Cas systems. Science 2013; 339(6121): 819– 823. doi: 10.1126/ science.1231143.

2. Lander ES. The Heroes of CRISPR. Cell 2016; 164(1– 2): 18– 28. doi: 10.1016/ j.cel­l.2015.12.041.

3. Gupta RM, Musunuru K. Expand­­ing the genetic edit­­ing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest 2014; 124(10): 4154– 4161. doi: 10.1172/ JCI72992.

4. Adli M. The CRISPR tool kit for genome edit­­ing and beyond. Nat Com­mun 2018; 9(1): 1911. doi: 10.1038/ s41467-018-04252-2.

5. Chen B, Gilbert LA, Cimini BA et al. Dynamic imag­­ing of genomic loci in liv­­ing human cel­ls by an optimized CRISPR/ Cas system. Cell 2013; 155(7): 1479– 1491. doi: 10.1016/ j.cel­l.2013.12.001.

6. Shachaf CM, Kopelman AM, Arvanitis C et al. MYC inactivation uncovers pluripotent dif­ferentiation and tumour dormancy in hepatocel­lular cancer. Nature 2004; 431(7012): 1112– 1117. doi: 10.1038/ nature03043.

7. 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– 8106. doi: 10.1128/ mcb.14.12.8096.

8. Klann TS, Black JB, Chel­lappan M et al. CRISPR-Cas9 epigenome edit­­ing enables high-throughput screen­­ing for functional regulatory elements in the human genome. Nat Biotechnol 2017; 35(6): 561– 568. doi: 10.1038/ nbt.3853.

9. Zatloukalova P, Pjechova M, Babcanova S et al. The role of PD-1/ PD-L1 signal­­ing pathway in antitumor im­mune response. Klin Onkol 2016; 29 (Suppl 4): 72– 77. doi: 10.14735/ amko20164S72.

10. Barber DL, Wher­ry EJ, Masopust D et al. Restor­­ing function in exhausted CD8 T cel­ls dur­­ing chronic viral infection. Nature 2006; 439(7077): 682– 687. doi: 10.1038/ nature04444.

11. Bif­fi A, Bartolomae CC, Cesana D et al. Lentiviral vector com­mon integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood 2011; 117(20): 5332– 5339. doi: 10.1182/ blood-2010-09-306761.

12. Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpret­­ing clinical outcomes to date. Blood 2016; 127(26): 3312– 3320. doi: 10.1182/ blood-2016-02-629063.

13. Xia AL, Wang XC, Lu YJ et al. Chimeric-antigen receptor T (CAR-T) cell ther­apy for solid tumors: chal­lenges and opportunities. Oncotarget 2017; 8(52): 90521– 90531. doi: 10.18632/ oncotarget.19361.

14. Eshhar Z, Waks T, Gross G et al. Specific activation and target­­ing of cytotoxic lymphocytes through chimeric single chains consist­­ing of antibody-bind­­ing domains and the gam­ma or zeta subunits of the im­munoglobulin and T-cell receptors. Proc Natl Acad Sci USA 1993; 90(2): 720– 724. doi: 10.1073/ pnas.90.2.720.

15. Eyquem J, Mansil­la-Soto J, Giavridis T et al. Target­­ing a CAR to the TRAC locus with CRISPR/ Cas9 enhances tumour rejection. Nature 2017; 543(7643): 113– 117. doi: 10.1038/ nature21405.

16. Tang Z, Qian M, Ho M. The role of mesothelin in tumor progres­sion and targeted ther­apy. Anticancer Agents Med Chem 2013; 13(2): 276– 280.

17. Ren J, Zhang X, Liu X et al. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget 2017; 8(10): 17002– 17011. doi: 10.18632/ oncotarget.15218.

Štítky
Paediatric clinical oncology Surgery Clinical oncology

Článok vyšiel v časopise

Clinical Oncology

Číslo Supplementum 3

2019 Číslo Supplementum 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#