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Smith, J., Rodriguez, T., Mou, H., Kwan, S-Y., Pratt, H., Zhang, X-O., Cao, Y., Liang, S., Ozata, D. M., Yu, T., Yin, Q., Hazeltine, M., Weng, Z., Sontheimer, E. J., Xue, W. (2020). YAP1 withdrawal in hepatoblastoma drives therapeutic differentiation of tumor cells to functional hepatocyte-like cells. Hepatology, in press. (PMID: 32452550)

Chatterjee, P., Lee, J., Nip, L., Koseki, S. R. T., Tysinger, E., Sontheimer, E. J., Jacobson, J. M. and Jakimo, N. (2020). A Cas9 with PAM recognition for adenine dinucleotides.  Nature Communications 11, 2474(PMID: 32424114)

Chatterjee, P., Jakimo, N., Lee, J., Amrani, N., Rodriguez, T., Koseki, S. R. T., Tysinger, E., Qing, R., Sontheimer, E. J. and Jacobson, J. (2020) An engineered ScCas9 with broad PAM range and high specificity and activity.  Nature Biotechnology, in press(PMID: 32393822)

Iyer, S., Mir, A., Vega-Badillo, J., Roscoe, B. P., Ibraheim, R., Zhu, L. J., Lee, J., Liu, P., Luk, K., Mintzer, E., Soares de Brito, J., Zamore, P. D., Sontheimer, E. J. and Wolfe, S. A. (2019) Efficient homology-directed repair with circular ssDNA donors.  Manuscript in revision. 

Ghanta, K. S., Dokshin, G. A., Mir, A., Shin, M., Medha, P., Edraki, A., Gneid, H., Lawson, N., Watts, J., Sontheimer, E. J., and Mello, C. C. (2019) 5’-Modified DNA donors are highly potent at low concentrations and improve efficiency of homology-directed genome editing. Manuscript in revision. 

Davidson, A. R., Lu, W.-T., Stanley, S.Y., Wang, J., Mejdani, M., Trost, C. N., Hicks, B.T., Lee, J. and Sontheimer, E. J.  (2020) Anti-CRISPRs: Protein inhibitors of CRISPR-Cas systems.  Annual Review of Biochemistry 89, 309-332. (PMID: 32186918)

Barrangou, R. and Sontheimer, E. J. (2020) CRISPR shields: Fending off diverse Cas nucleases with nucleus-like structures.  Fending off diverse Cas nucleases with nucleus-like structures. Molecular Cell 77, 934-935. (PMID: 32142691)

Sun, W., Yang, J., Cheng, Z., Amrani, N., Liu, C., Wang, K., Ibraheim, R., Edraki, A., Huang, X., Wang, M., Wang, J., Liu, L., Sheng, G., Yang, Y., Liu, J., Sontheimer, E. J., and Wang, Y. (2019) Structures of Neisseria meningitidis Cas9 complexes in catalytically poised and anti-CRISPR-inhibited states. Molecular Cell 76, 938-952. (PMID: 31668930)

Garcia, B., Lee, J., Edraki, A., Hidalgo-Reyes, Y., Erwood, S., Mir, A., Trost, C., Seroussi, U., Stanley, S. Y., Cohn, R. D., Claycomb, J. M., Sontheimer, E. J., Maxwell, K. L. and Davidson, A. R. (2019) Anti-CRISPR AcrIIA5 potently inhibits all Cas9 homologs used for genome editing. Cell Reports 29, 1739-1746.  (PMID: 31722192)

Lee, J., Mou, H., Ibraheim, R., Liang, S.-Q., Xue, W., and Sontheimer, E. J. (2019) Tissue-specific genome editing in vivo by microRNA-repressible anti-CRISPR proteins. RNA 25, 1421-1431. (PMID: 31439808)

Sontheimer, E. J. (2019) X-Tracting a new CRISPR-Cas genome-editing platform from metagenomic data sets. The CRISPR Journal 2, 148-150.  (PMID: 31225753)

Thavalingam, A., Cheng, Z., Garcia, B., Huang, X., Shah, M., Sun, W., Wang, M., Harrington, L., Hwang, S., Hidalgo-Reyes, Y., Sontheimer, E. J., Doudna, J. A., Davidson, A. R., Moraes, T. F., Wang, Y., and Maxwell, K. L. (2019) Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anit-CRISPR AcrIIC2 Nature Communications 10, 2806. (PMID: 31243272)

Edraki, A., Mir, A., Ibraheim, R., Gainetdinov, I., Yoon, Y., Gallant, J., Song, C.-Q., Cao, Y., Xue, W., Rivera-Pérez, J. A., and Sontheimer, E. J. (2019) A compact, high-accuracy Cas9 with a dinucleotide PAM for in vivo genome editing. Molecular Cell 73, 714-726. (PMID: 30581144)

Gao, X. D., Rodriguez, T., and Sontheimer, E. J. (2018) Adapting dCas9-APEX2 for subnuclear proteomic profiling. Methods in Enzymology 616, 365-383. (PMID: 30691651)

Amrani, N., Gao, X. D., Liu, P., Edraki, A., Mir, A., Ibraheim, R., Gupta, A., Sasaki, K. E., Wu, T., Donohoue, P. D., Settle, A. H., Lied, A. M., McGovern, K., Fuller, C. K., Cameron, P., Fazzio, T. G., Zhu, L. J., Wolfe, S. A., and Sontheimer, E. J. (2018) NmeCas9 is an intrinsically high-fidelity genome editing platform. Genome Biology 19, 214. (PMID: 30518407)

Lee, J., Mir, A., Edraki, A., Garcia, B., Amrani, N., Lou, H. E., Gainetdinov, I., Pawluk, A., Ibraheim, R., Gao, X. D., Liu, P., Davidson, A. R., Maxwell, K. L., and Sontheimer, E. J. (2018) Potent Cas9 inhibition in bacterial and human cells by AcrIIC4 and AcrIIC5 anti-CRISPR proteins. mBio 9, e02321-18. (PMID: 30514786)

Bolukbasi, M. F., Liu, P., Luk, K., Kwok, S. F., Gupta, A., Amrani, N., Sontheimer, E. J., Zhu, L. J., and Wolfe, S. A. (2018) Orthogonal Cas9-Cas9 chimeras provide a versatile platform for genome editing. Nature Communications 9, 4856. (PMID: 30531933)

Bondy-Denomy, J., Davidson, A. R., Doudna, J. A., Fineran, P. C., Maxwell, K. L., Moineau, S., Peng, X., Sontheimer, E. J., and Weidenheft, B. (2018) A unified resource for tracking anti-CRISPR names. The CRISPR Journal 1, 304-305. (PMID: 31021273)

Ibraheim, R., Song, C.-Q., Mir, A., Amrani, N., Xue, W., and Sontheimer, E. J. (2018) All-in-one Adeno-associated Virus Delivery and Genome Editing by Neisseria meningitidis Cas9 in vivo. Genome Biology 19, 137. (PMID: 30231914)

Mir, A., Alterman, J. A., Hassler, M. R., Debacker, A. J., Hudgens, E., Echevarria, D., Brodsky, M. H., Khvorova, A., Watts, J. K., and Sontheimer, E. J. (2018) Heavily and fully modified RNAs guide efficient SpyCas9-mediated genome editing. Nature Communications 9, 2641. (PMID: 29980686)

Stone, N., Hilbert, B. J., Hidalgo, D., Halloran, K. T., Lee, J., Sontheimer, E. J., and Kelch, B. A. (2018) A hyperthermophilic phage decoration protein suggests common evolutionary origin with herpesvirus triplex proteins and an anti-CRISPR protein. Structure 26, 936-947. (PMID: 29779790)

Gao, X. D., Tu, L.-C., Mir, A., Rodriguez, T., Ding, Y., Leszyk, J., Dekker, J., Shaffer, S. A., Zhu, L. J., Wolfe, S. A., and Sontheimer, E. J. (2018) C-BERST: Defining subnuclear proteomic landscapes at genomic elements with dCas9-APEX2. Nature Methods 15, 433-436. (PMID: 29735996)

Edraki, A., and Sontheimer, E. J. (2018) CRISPRs from scratch. Nature Microbiology 3, 261-262. (PMID: 29463924)

Mir, A., Edraki, A., Lee, J., and Sontheimer, E. J. (2018) Type II-C CRISPR-Cas9 biology, mechanism and application. ACS Chemical Biology 13, 357-365. (PMID: 29202216)

Harrington, L. B., Doxzen, K. W., Ma, E., Liu, J.-J., Knott, G. J., Edraki, A., Amrani, N., Chen, J. S., Cofsky, J. C., Kranzusch, P. J., Sontheimer, E. J., Davidson, A. R., Maxwell, K., and Doudna, J. A. (2017). A broad-spectrum inhibitor of CRISPR-Cas9. Cell 170, 1224-1233. (PMID: 28844692)

Sontheimer, E. J. and Davidson, A. R. (2017) Inhibition of CRISPR-Cas systems by mobile genetic elements. Current Opinion in Microbiology 37, 120-127. (PMID: 28668720)

Mou, H., Smith, J. L., Yin, H., Peng, L., Moore, J., Zhang, X.-O., Song, C.-Q., Sheel, A., Wu, Q., Ozata, D. M., Li, Y., Anderson, D. G., Emerson, C. P., Sontheimer, E. J., Moore, M. J., Weng, Z., and Xue, W. (2017) CRISPR-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Genome Biology 18, 108. (PMID: 28615073)

Pawluk, A., Amrani, N., Zhang, Y., Garcia, B., Hidalgo-Reyes, Y., Lee, J., Edraki, A., Shah, M., Sontheimer, E. J., Maxwell, K., and Davidson, A. R. (2016) Naturally occurring off-switches for CRISPR-Cas9. Cell 167, 1829-1838. (PMID: 27984730)

Sontheimer, E. J. and Marraffini, L. A. (2016) CRISPR goes retro. Science 351, 920-921. (PMID:26917756

Sontheimer, E. J. and Wolfe, S. A. (2015) Cas9 gets a classmate. Nature Biotechnology 33, 1240-1241. (PMID: 26650011)

Zhang, Y., Rajan, R., Seifert, H. S., Mondragón, A. and Sontheimer, E. J. (2015) DNase H activity of Neisseria meningitidis Cas9. Molecular Cell 60, 242-255. (PMID: 26474066)

Wakefield, N., Rajan, R. and Sontheimer, E. J. (2015) Primary processing of CRISPR RNA by the endonuclease Cas6 in Staphylococcus epidermidis. FEBS Letters 589, 3197-3204. (PMID: 26364721)

Wang, D., Mou, H., Li, S., Li, Y., Hough, S., Tran, K., Li, J., Yin, H., Anderson, D. G., Sontheimer, E. J., Weng, Z., Gao, G. and Xue, W. (2015) Adenovirus-mediated somatic genome editing of Pten by CRISPR/Cas9 in mouse liver in spite of Cas9-specific immune responses. Human Gene Therapy 26, 432-442. (PMID: 26086867)

Sontheimer, E. J. and Barrangou, R. (2015) The bacterial origins of the CRISPR genome editing revolution. Human Gene Therapy 26, 413-424. (PMID: 26078042)

Doudna, J. A. and Sontheimer, E. J., Editors (2014) The use of CRISPR-Cas9, ZFNs, and TALENs in generating site-specific genome alterations. Methods in Enzymology, Volume 516. (PMID: 25398356)

Zhang, Y. and Sontheimer, E.J. (2014) Cascading into focus. Science 345, 1452-1453. (PMID: 25237089)

Hurtado, S. B., Kim Guisbert, K. S. and Sontheimer, E. J. (2014) SPO24 is a transcriptionally dynamic, small ORF-encoding locus required for efficient sporulation in S. cerevisiae. PLoS ONE 9(8), e105058. (PMID: 25127041)

Hou, Z., Zhang, Y., Propson, N. E., Howden, S. E., Chu, L.-F., Sontheimer, E. J. and Thomson, J. A. (2013) Efficient genome engineering in human pluripotent stem cells using Cas9 from Neisseria meningitidis. Proceedings of the National Academy of Sciences U.S.A. 110, 15644-15649. (PMID: 23940360)

Zhang, Y., Heidrich, N., Joseph, B., Gunderson, C. Seifert, H. S., Schoen, C., Vogel, J. and Sontheimer, E. J. (2013) Processing-independent CRISPR RNAs limit natural transformation in Neisseria meningitidis. Molecular Cell 50, 488-503. (PMID: 23706818)

Kim Guisbert, K. S. and Sontheimer, E. J. (2013) Quit stalling or you’ll be silenced. Cell 152, 938-939. (PMID: 23452843)

Sontheimer, E. J. (2012) Small RNAs of opposite sign…but same absolute value. Cell 151, 1157-1158. (PMID: 23217700)

Kim Guisbert, K. S., Zhang, Y., Flatow, J., Hurtado, S., Staley, J. P., Lin, S. and Sontheimer, E. J. (2012) Meiosis-induced alterations in transcript architecture and noncoding RNA expression in S. cerevisiae. RNA 18, 1142-1153. (PMID: 22539527)

Gerbasi, V. R., Preall, J. B., Golden, D. E., Powell, D. W., Cummins, T. D. and Sontheimer, E. J. (2011) Blanks, a nuclear siRNA/dsRNA binding complex component, is required for Drosophila spermiogenesis. Proceedings of the National Academy of Sciences U.S.A. 108, 3204-3209. (PMID: 21300896)

Sontheimer, E. J. and Marraffini, L. A. (2010) Microbiology: Slicer for DNA. Nature 468, 45-46. (PMID: 21048757)

Gerbasi, V. R., Golden, D. E., Hurtado, S. B. and Sontheimer, E. J. (2010) Proteomic identification of Drosophila siRNA-associated factors. Molecular & Cellular Proteomics 9, 1866-1872. (PMID: 20472918)

Marraffini, L. A. and Sontheimer, E. J. (2010) CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nature Reviews Genetics 11, 181-190. (PMID: 20125085)

Marraffini, L. A. and Sontheimer, E. J. (2010) Self vs. non-self discrimination during CRISPR RNA-directed immunity. Nature 463, 568-571. (PMID: 20072129)

Marraffini, L. A. and Sontheimer, E. J. (2009) Invasive DNA, chopped and in the CRISPR. Structure 17, 786-787. (PMID: 19523896)

Lee, Y. S., Pressman, S., Andress, A. P., Kim, K., White, J. L., Cassidy, J. J., Li, X., Lubell, K., Lim, D. H., Cho, I. S., Nakahara, K., Preall, J. B., Bellare, P., Sontheimer, E. J. and Carthew, R. W. (2009) Silencing by small RNAs is linked to endosome trafficking. Nature Cell Biology 11, 1150-1156. (PMID: 19684574)

Carthew, R. W., and Sontheimer, E. J. (2009) Origins and mechanisms of siRNAs and miRNAs. Cell 136, 642-655. (PMID: 19239886)

Marraffini, L. A. and Sontheimer, E. J. (2008) CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322, 1843-1845. (PMID: 19095942)

Bellare, P., Small, E. C., Huang, X., Wohlschlegel, J. A., Staley, J. P. and Sontheimer, E. J. (2008) A role for ubiquitin in the spliceosome assembly pathway. Nature Structural & Molecular Biology 15, 444-451. (PMID: 18425143)

Golden, D. E., Gerbasi, V. R., and Sontheimer, E. J. (2008) An inside job for siRNAs. Molecular Cell 31, 309-312. (PMID: 18691963)

Bellare, P., and Sontheimer, E. J. (2007) A fork in the road for microRNAs. Nature Structural & Molecular Biology 14, 684-686. (PMID: 17676029)

Preall, J. B., He, Z., Gorra, J. and Sontheimer, E. J. (2006). Short interfering RNA strand selection is independent of double-stranded RNA processing polarity during RNA interference in Drosophila. Current Biology 16, 530-535. (PMID: 16527750)

Bellare, P., Kutach, A. K., Rines, A., Guthrie, C. and Sontheimer, E. J. (2006). Ubiquitin binding by a variant Jab1/MPN domain in the essential pre-mRNA splicing factor Prp8p. RNA 12, 292-302. (PMID: 16428608)

Pham, J. W. and Sontheimer, E. J. (2005). Molecular requirements for RNA-induced silencing complex assembly in the Drosophila RNA interference pathway. Journal of Biological Chemistry 280, 39278-39283. (PMID: 16179342)

Preall, J. B., and Sontheimer, E. J. (2005). RNAi: RISC gets loaded. Cell 123, 543-545. (PMID: 16286001)

Sontheimer, E. J., and Carthew, R. W. (2005). Silence from within: Endogenous siRNAs and miRNAs. Cell 122, 9-12. (PMID: 16009127)

Pham, J. W., and Sontheimer, E. J. (2005). Separation of Drosophila RNA silencing complexes by native gel electrophoresis. In “Methods in Molecular Biology, vol. 309: RNA Silencing: Methods and Protocols” (ed. G. G. Carmichael), pp. 11-16. Humana Press, Totowa, New Jersey. (PMID: 15990394)

Sontheimer, E. J. (2005). Assembly and function of RNA silencing complexes. Nature Reviews Molecular Cell Biology 6, 127-138. (PMID: 15654322)

Pellino, J. L., Jaskiewicz, L., Filipowicz, W. and Sontheimer, E. J. (2005). ATP modulates siRNA interactions with an endogenous human Dicer complex. RNA 11, 1719-1724. (PMID: 16177131)

Pham, J. W., Radhakrishnan, I. and Sontheimer, E. J. (2004). Thermodynamic and structural characterization of 2’-nitrogen-modified RNA duplexes. Nucleic Acids Research 32, 3446-3455. (PMID: 15247335)

Sontheimer, E. J., and Carthew, R. W. (2004). Argonaute journeys into the heart of RISC. Science 305, 1409-1410. (PMID: 15353786)

Pham, J. W., and Sontheimer, E. J. (2004). The making of an siRNA. Molecular Cell 15, 163-164. (PMID: 15260964)

He, Z., and Sontheimer, E. J. (2004). “siRNAs and miRNAs”: A meeting review on RNA silencing. RNA 10, 1165-1173. (PMID: 15272116)

Pham, J. W., Pellino, J. L., Lee, Y. S., Carthew, R. W. and Sontheimer, E. J. (2004). A Dicer-2-dependent 80S complex cleaves targeted mRNAs during RNAi in Drosophila. Cell 117, 83-94. (PMID: 15066284)

Lee, Y. S., Nakahara, K., Pham, J. W., Kim, K., He, Z., Sontheimer, E. J. and Carthew, R. W. (2004). Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117, 69-81. (PMID: 15066283)

Pellino, J. L. and Sontheimer, E. J. (2003). R2D2 leads the silencing trigger to mRNA's death star. Cell 115, 132-133. (PMID: 14567910)

Sontheimer, E. J. (2001). The spliceosome shows its metal. Nature Structural Biology 8, 11-13. (PMID: 11135658)

Gordon, P. M., Sontheimer, E. J. and Piccirilli, J. A. (2000). Kinetic characterization of the second step of group II intron splicing: Role of metal ions and the cleavage site 2’-OH in catalysis. Biochemistry 39, 12939-12952. (PMID: 11041859)

Gordon, P. M., Sontheimer, E. J. and Piccirilli, J. A. (2000). Metal ion catalysis during the exon ligation step of nuclear pre-mRNA splicing: Extending the parallels between the spliceosome and group II introns. RNA 6, 199-205. (PMID: 10688359)

Warnecke, J. M., Sontheimer, E. J., Piccirilli, J. A. and Hartmann, R. K. (2000). Active site constraints in the hydrolysis reaction catalyzed by bacterial RNase P: Analysis of precursor tRNAs with a single 3’-S-phosphorothiolate internucleotide linkage. Nucleic Acids Research 28, 720-727. (PMID: 10637323)

Sontheimer, E. J., Gordon, P. M. and Piccirilli, J. A. (1999). Metal ion catalysis during group II intron self-splicing: Parallels with the spliceosome. Genes and Development 13, 1729-1741. (PMID: 10398685)

Sontheimer, E. J. (1999). Bridging sulfur substitutions in the analysis of pre-mRNA splicing. Methods 18, 29-37. (PMID: 10208814)

Sontheimer, E. J., Sun, S. and Piccirilli, J. A. (1997). Metal ion catalysis during splicing of premessenger RNA. Nature 388, 801-805. (PMID: 9285595)

Sontheimer, E. J.  (1994). Site-specific RNA crosslinking with 4-thiouridine. Molecular Biology Reports 20, 35-44. (PMID: 7531281)

Sontheimer, E. J. and Steitz, J. A. (1993). The U5 and U6 small nuclear RNAs as active site components of the spliceosome. Science 262, 1989-1996. (PMID: 8266094)

Cortes, J. J., Sontheimer, E. J., Seiwert, S. D. and Steitz, J. A. (1993). Mutations in the conserved loop of human U5 snRNA generate use of novel cryptic 5' splice sites in vivo. EMBO Journal 12, 5181-5189. (PMID: 8262061)

Wyatt, J. R., Sontheimer, E. J. and Steitz, J. A. (1992). Site-specific crosslinking of mammalian U5 snRNP to the 5' splice site prior to the first step of premessenger RNA splicing. Genes and Development 6, 2542-2553. (PMID: 1340469)

Gelpi, C., Sontheimer, E. J. and Rodriguez-Sanchez, J. L. (1992). Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion. Proceedings of the National Academy of Sciences U.S.A. 89, 9739-9743. (PMID: 1409691

Sontheimer, E. J. and Steitz, J. A. (1992). Three novel functional variants of human U5 small nuclear RNA. Molecular and Cell Biology12, 734-746. (PMID: 1310151)

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  • Anti-CRISPR AcrIIA5 Potently Inhibits All Cas9 Homologs Used for Genome Editing.

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    Anti-CRISPR AcrIIA5 Potently Inhibits All Cas9 Homologs Used for Genome Editing.

    Cell Rep. 2019 11 12;29(7):1739-1746.e5

    Authors: Garcia B, Lee J, Edraki A, Hidalgo-Reyes Y, Erwood S, Mir A, Trost CN, Seroussi U, Stanley SY, Cohn RD, Claycomb JM, Sontheimer EJ, Maxwell KL, Davidson AR

    CRISPR-Cas9 systems provide powerful tools for genome editing. However, optimal employment of this technology will require control of Cas9 activity so that the timing, tissue specificity, and accuracy of editing may be precisely modulated. Anti-CRISPR proteins, which are small, naturally occurring inhibitors of CRISPR-Cas systems, are well suited for this purpose. A number of anti-CRISPR proteins have been shown to potently inhibit subgroups of CRISPR-Cas9 systems, but their maximal inhibitory activity is generally restricted to specific Cas9 homologs. Since Cas9 homologs vary in important properties, differing Cas9s may be optimal for particular genome-editing applications. To facilitate the practical exploitation of multiple Cas9 homologs, here we identify one anti-CRISPR, called AcrIIA5, that potently inhibits nine diverse type II-A and type II-C Cas9 homologs, including those currently used for genome editing. We show that the activity of AcrIIA5 results in partial in vivo cleavage of a single-guide RNA (sgRNA), suggesting that its mechanism involves RNA interaction.

    PMID: 31722192 [PubMed - indexed for MEDLINE]

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