CRISPR/Cas9 dengan Dual-sgRNAs Bertarget Gen E6 dan E7 Virus HPV 16 Sebagai Inovasi Terapi Gen Upaya Menurunkan Angka Kanker Serviks Global

Fachreza Aryo Damara(1*),

(1) Fakultas Kedokteran Universitas Padjadjaran
(*) Corresponding Author




DOI: https://doi.org/10.26858/ijfs.v3i2.4779

Abstract


Kanker serviks merupakan kanker dengan insidensi terbesar kedua pada wanita di dunia. 80% dari kasus kanker serviks terjadi pada negara berkembang. Sebanyak 62% dari kasus kanker serviks disebabkan oleh virus Human Papilloma Virus (HPV) tipe 16.  Hingga saat ini, keterbatasan dan efek samping dari tatalaksana kemoterapi dan radioterapi terhadap pasien kanker serviks menyebabkan masih dibutuhkannya inovasi terapi yang lebih efektif dan terjangkau. CRISPR/Cas9 telah menjadi pendekatan terapi gen yang efektif dan spesifik serta memakan biaya produksi yang kecil dengan mengintervensi DNA target terhadap berbagai penyakit termasuk kanker. Tujuan dari makalah ini adalah untuk membahas potensi dari inovasi terapi gen menggunakan CRISPR/Cas9 dengan dual-sgRNAs bertarget delesi gen E6 dan E7 pada virus HPV16 terhadap pasien kanker serviks. Makalah ini disusun dengan metode tinjauan pustaka dengan menganalisa dan sinstesis dari berbagai referensi yang sesuai dengan kata kunci. Hasil  peneltian terhadap delesi gen E6 dan E7 pada HPV16 secara terpisah menunjukkan terjadinya penurunan ukuran tumor yang signifikan dan menginduksi proses apoptosis dari sel kanker serviks. Sehingga penggunaan dual-sgRNAs bertarget kedua gen pada HPV16 dapat menjadi terapi efektif dan terjangkau terhadap pasien kanker serviks untuk menurunkan angka kasus kanker serviks global.


Full Text:

PDF

References


National Cancer Institute (NIH). 2014 Cervical Cancer Treatment. NCI. https://www.cancer.gov/types/cervical/patient/cervical-treatment-pdq

World Health Organization (WHO). 2016 Human papillomavirus (HPV) and cervical cancer fact sheet. WHO. http://www.who.int/mediacentre/factsheets/fs380/en/

Kementrian Kesehatan Republik Indonesia (Kemenkes RI). 2016. InfoDATIN : Pusat Data dan Informasi Kementerian Kesehatan RI. Kemenkes RI.

Kementrian Kesehatan Republik Indonesia (Kemenkes RI). 2016. Panduan Penatalsanaan Kanker Serviks. Komite Penanggulangan Kanker Nasional.

Castellsagué, X. 2008. Natural history and epidemiology of HPV infection and cervical cancer. Gynecologic oncology, 110(3), S4-S7.

de Sanjose, S., Quint, W. G., Alemany, L., Geraets, D. T.,

Klaustermeier, J. E., Lloveras, B., ... & Vallejos, C. S. 2010. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. The lancet oncology, 11(11), 1048-1056.

Wong, L. P., Wong, Y. L., Low, W. Y., Khoo, E. M., & Shuib, R. 2009. Knowledge and awareness of cervical cancer and screening among Malaysian women who have never had a Pap smear: a qualitative study. Singapore medical journal, 50(1), 49.

National Cancer Institute. 2010 Radiation Therapy for Cancer. NCI. https://www.cancer.gov/about-cancer/treatment/types/radiation-therapy

Xia, S., Zhao, Y., Yu, S., & Zhang, M. 2010. Activated PI3K/Akt/COX-2 pathway induces resistance to radiation in human cervical cancer HeLa cells. Cancer biotherapy & radiopharmaceuticals, 25(3), 317-323.

Shi, M., Du, L., Liu, D., Qian, L., Hu, M., Yu, M., ... & Wang, L. 2012. Glucocorticoid regulation of a novel HPV–E6–p53–miR‐145 pathway modulates invasion and therapy resistance of cervical cancer cells. The Journal of pathology, 228(2), 148-157.

Ginn, S. L., Alexander, I. E., Edelstein, M. L., Abedi, M. R., & Wixon, J. 2013. Gene therapy clinical trials worldwide to 2012–an update. The journal of gene medicine, 15(2), 65-77.

Doudna, J. A., & Charpentier, E. 2014. The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096.

Wiedenheft, B., Zhou, K., Jinek, M., Coyle, S. M., Ma, W., & Doudna, J. A. 2009. Structural basis for DNase activity of a conserved protein implicated in CRISPR-mediated genome defense. Structure, 17(6), 904-912.

Jore, M. M., Lundgren, M., Van Duijn, E., Bultema, J. B., Westra, E. R., Waghmare, S. P., ... & Beijer, M. R. (2011). Structural basis for CRISPR RNA-guided DNA recognition by Cascade. Nature structural & molecular biology, 18(5), 529-536.

Narisawa‐Saito, M., & Kiyono, T. 2007. Basic mechanisms of high‐risk human papillomavirus‐induced carcinogenesis : Roles of E6 and E7 proteins. Cancer science, 98(10), 1505-1511.

Beaudenon, S., & Huibregtse, J. M. 2008. HPV E6, E6AP and cervical cancer. BMC biochemistry, 9(1), S4.

Teissier, S., Khalifa, Y. B., Mori, M., Pautier, P., Desaintes, C., & Thierry, F. 2007. A new E6/P63 pathway, together with a strong E7/E2F mitotic pathway, modulates the transcriptome in cervical cancer cells. Journal of virology, 81(17), 9368-9376.

McLaughlin-Drubin, M. E., & Münger, K. 2009. The human papillomavirus E7 oncoprotein. Virology, 384(2), 335-344.

Garneau, J. E., Dupuis, M. E., Villion, M., Romero, D. A., Barrangou, R., Boyaval, P., ... & Moineau, S. 2010. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature, 468(7320), 67-71.

Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., ... & Zhang, F. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science, 339(6121), 819-823.

Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. 2013. Genome engineering using the CRISPR-Cas9 system. Nature protocols, 8(11), 2281-2308.

Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., & Charpentier, E. 2012. A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science, 337(6096), 816-821.

Cencic, R., Miura, H., Malina, A., Robert, F., Ethier, S., Schmeing, T. M., ... & Pelletier, J. 2014. Protospacer adjacent motif (PAM)-distal sequences engage CRISPR Cas9 DNA target cleavage. PloS one, 9(10), e109213.

Sander, J. D., & Joung, J. K. 2014. CRISPR-Cas systems for editing, regulating and targeting genomes. Nature biotechnology, 32(4), 347-355.

Marraffini, L. A., & Sontheimer, E. J. 2010. Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature, 463(7280), 568-571.

Zhen, S., Hua, L., Takahashi, Y., Narita, S., Liu, Y. H., & Li, Y. 2014. In vitro and in vivo growth suppression of human papillomavirus 16-positive cervical cancer cells by CRISPR/Cas9. Biochemical and biophysical research communications, 450(4), 1422-1426.

Kennedy, E. M., Kornepati, A. V., Goldstein, M., Bogerd, H. P., Poling, B. C., Whisnant, A. W., ... & Cullen, B. R. 2014. Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. Journal of virology, 88(20), 11965-11972.


Article Metrics

Abstract view : 1261 times | PDF view : 541 times

Refbacks

  • There are currently no refbacks.




Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.



Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.