Preprint / Version 1

The Birth of CRISPR/Cas9


  • Bianca Bolocan Issaquah High School



CRISPR, Cas9, Cas13, Genetic Engineering, CRISPR/Cas9, CRISPR/Cas13, History of CRISPR


CRISPR/Cas9 is a very important component of genetic engineering, originating from the
immune system of bacteria. It is far more efficient than any other method discovered as of 2023.

Despite this, however, many people interested in this tool are not aware of how it was
discovered and adapted. There are several contributors who helped build CRISPR/Cas9 into
what it is today, from Francisco Mojica, who discovered the system, to Le Cong, who identified
its purpose, and finally, Feng Zhang, who adapted the system for humans. This paper will
discuss the history of CRISPR, from its discovery to its uses today, along with how it continues
to be developed.


Bier, E. (2021). Gene drives gaining speed. Nature Reviews Genetics, 23(1), 5–22.

Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T.,

Nickstadt, A., & Bonas, U. (2009). Breaking the code of DNA binding specificity of tal-type

III effectors. Science, 326(5959), 1509–1512.

Bolotin, A., Quinquis, B., Sorokin, A., & Ehrlich, S. D. (2005). Clustered regularly

interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal

origin. Microbiology, 151(8), 2551–2561.

Caso, F., & Davies, B. (2021). Base editing and prime editing in Laboratory Animals.

Laboratory Animals, 56(1), 35–49.

Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang,

W., Marraffini, L. A., & Zhang, F. (2013). Multiplex Genome Engineering using

CRISPR/Cas Systems. Science, 339(6121), 819–823.

Durai, S. (2005). Zinc finger nucleases: Custom-designed molecular scissors for Genome

Engineering of plant and mammalian cells. Nucleic Acids Research, 33(18), 5978–5990.

Garrood, W. T., Cuber, P., Willis, K., Bernardini, F., Page, N. M., & Haghighat-Khah, R. E.

(2022). Driving down malaria transmission with engineered gene drives. Frontiers in

Genetics, 13.

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. 7

Lander, E. S. (2016). The heroes of CRISPR. Cell, 164(1–2), 18–28.

Mojica, F. J., Juez, G., & Rodriguez‐Valera, F. (1993). Transcription at different salinities

of haloferax mediterranei sequences adjacent to partially modified pstI sites. Molecular

Microbiology, 9(3), 613–621.

Mojica, F.J.M., Ferrer, C., Juez, G., & Rodríguez‐Valera, F. (1995). Long stretches of

short tandem repeats are present in the largest replicons of the archaea haloferax

mediterranei and haloferax volcanii and could be involved in replicon partitioning.

Molecular Microbiology, 17(1), 85–93.

Mojica, Francisco J.M., Díez-Villaseñor, C., García-Martínez, J., & Soria, E. (2005).

Intervening sequences of regularly spaced prokaryotic repeats derive from foreign

genetic elements. Journal of Molecular Evolution, 60(2), 174–182.

Pourcel, C., Salvignol, G., & Vergnaud, G. (2005). CRISPR elements in yersinia pestis

acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional

tools for evolutionary studies. Microbiology, 151(3), 653–663.

Sulis, D. B., Jiang, X., Yang, C., Marques, B. M., Matthews, M. L., Miller, Z., Lan, K.,

Cofre-Vega, C., Liu, B., Sun, R., Sederoff, H., Bing, R. G., Sun, X., Williams, C. M.,

Jameel, H., Phillips, R., Chang, H., Peszlen, I., Huang, Y.-Y., … Wang, J. P. (2023).

Multiplex CRISPR editing of wood for Sustainable Fiber Production. Science, 381(6654),


Tong, H., Huang, J., Xiao, Q., He, B., Dong, X., Liu, Y., Yang, X., Han, D., Wang, Z.,

Wang, X., Ying, W., Zhang, R., Wei, Y., Xu, C., Zhou, Y., Li, Y., Cai, M., Wang, Q., Xue,

M., … Yang, H. (2022). High-fidelity CAS13 variants for targeted RNA degradation with

minimal collateral effects. Nature Biotechnology, 41(1), 108–119.

Zhang, F., Cong, L., Lodato, S., Kosuri, S., Church, G. M., & Arlotta, P. (2011). Efficient

construction of sequence-specific tal effectors for modulating mammalian transcription.

Nature Biotechnology, 29(2), 149–153. ID NCT03057912, ID NCT03745287,