{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:32:00Z","timestamp":1786991520792,"version":"build-2736575974"},"reference-count":59,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/100000165","name":"Division of Chemistry","doi-asserted-by":"publisher","award":["CHE-1351807"],"award-info":[{"award-number":["CHE-1351807"]}],"id":[{"id":"10.13039\/100000165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["F32 CA180653"],"award-info":[{"award-number":["F32 CA180653"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["F32 CA239362"],"award-info":[{"award-number":["F32 CA239362"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA188228"],"award-info":[{"award-number":["R01 CA188228"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006064","name":"Sontag Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006064","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006919","name":"Massachusetts Institute of Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006919","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008126","name":"Dana-Farber\/Harvard Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008126","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gray Matters Brain Cancer Foundation"},{"DOI":"10.13039\/100016872","name":"Koch Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016872","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Antisense oligonucleotide therapies are important cancer treatments, which can suppress genes in cancer cells that are critical for cell survival. SF3B1 has recently emerged as a promising gene target that encodes a key splicing factor in the SF3B protein complex. Over 10% of cancers have lost one or more copies of the SF3B1 gene, rendering these cancers vulnerable after further suppression. SF3B1 is just one example of a CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) gene, but over 120 additional candidate CYCLOPS genes are known. Antisense oligonucleotide therapies for cancer offer the promise of effective suppression for CYCLOPS genes, but developing these treatments is difficult due to their limited permeability into cells and poor cytosolic stability. Here, we develop an effective approach to suppress CYCLOPS genes by delivering antisense peptide nucleic acids (PNAs) into the cytosol of cancer cells. We achieve efficient cytosolic PNA delivery with the two main nontoxic components of the anthrax toxin: protective antigen (PA) and the 263-residue N-terminal domain of lethal factor (LFN). Sortase-mediated ligation readily enables the conjugation of PNAs to the C terminus of the LFN protein. LFN and PA work together in concert to translocate PNAs into the cytosol of mammalian cells. Antisense SF3B1 PNAs delivered with the LFN\/PA system suppress the SF3B1 gene and decrease cell viability, particularly of cancer cells with partial copy-number loss of SF3B1. Moreover, antisense SF3B1 PNAs delivered with a HER2-binding PA variant selectively target cancer cells that overexpress the HER2 cell receptor, demonstrating receptor-specific targeting of cancer cells. Taken together, our efforts illustrate how PA-mediated delivery of PNAs provides an effective and general approach for delivering antisense PNA therapeutics and for targeting gene dependencies in cancer.<\/jats:p>","DOI":"10.1021\/acschembio.9b01027","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T15:25:35Z","timestamp":1588173935000},"page":"1358-1369","source":"Crossref","is-referenced-by-count":14,"title":["Targeting Cancer Gene Dependencies with Anthrax-Mediated\nDelivery of Peptide Nucleic Acids"],"prefix":"10.1021","volume":"15","author":[{"given":"Zeyu","family":"Lu","sequence":"first","affiliation":[{"name":"Massachusetts Institute of Technology , , 77 Massachusetts Avenue , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenton R.","family":"Paolella","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , , ,","place":["Boston, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-685X","authenticated-orcid":true,"given":"Nicholas L.","family":"Truex","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology , , 77 Massachusetts Avenue , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Loftis","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology , , 77 Massachusetts Avenue , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liao","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology , , 77 Massachusetts Avenue , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Rabideau","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology , , 77 Massachusetts Avenue , , ,","place":["Cambridge, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , , ,","place":["Boston, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Busanovich","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , , ,","place":["Boston, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rameen","family":"Beroukhim","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute , , , , ,","place":["Boston, Massachusetts, United States, 02139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-801X","authenticated-orcid":true,"given":"Bradley L.","family":"Pentelute","sequence":"additional","affiliation":[{"name":"Massachusetts Institute of Technology , , 77 Massachusetts Avenue , , ,","place":["Cambridge, Massachusetts, United States, 02139"]},{"name":"Massachusetts Institute of Technology , , , , ,","place":["Cambridge, Massachusetts, United States, 02139"]},{"name":"Broad Institute of MIT and Harvard , , ,","place":["Cambridge, Massachusetts, United States, 02142"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"2026081714194917200_cit1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1517\/13543776.2014.863874","article-title":"Peptide nucleic\nacids: A review on recent patents and technology transfer","volume":"24","author":"Gambari","year":"2014","journal-title":"Expert Opin. Ther. Pat."},{"key":"2026081714194917200_cit2","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1016\/j.cell.2012.07.023","article-title":"Cancer vulnerabilities\nunveiled by genomic loss","volume":"150","author":"Nijhawan","year":"2012","journal-title":"Cell"},{"key":"2026081714194917200_cit3","doi-asserted-by":"publisher","first-page":"e23268","DOI":"10.7554\/eLife.23268","article-title":"Copy-number\nand gene dependency analysis reveals partial copy loss of wild-type\nsf3b1 as a novel cancer vulnerability","volume":"6","author":"Paolella","year":"2017","journal-title":"eLife"},{"key":"2026081714194917200_cit4","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.ccell.2018.03.007","article-title":"Genomic\nand functional approaches to understanding\ncancer aneuploidy","volume":"33","author":"Taylor","year":"2018","journal-title":"Cancer Cell"},{"key":"2026081714194917200_cit5","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/nature07385","article-title":"Comprehensive\ngenomic characterization defines human glioblastoma genes and core\npathways","volume":"455","author":"Mclendon","year":"2008","journal-title":"Nature"},{"key":"2026081714194917200_cit6","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1056\/NEJMoa1109016","article-title":"Sf3b1 and other novel cancer genes in chronic lymphocytic leukemia","volume":"365","author":"Wang","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2026081714194917200_cit7","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/ng.2523","article-title":"Recurrent mutations at codon 625 of the splicing factor\nsf3b1 in uveal melanoma","volume":"45","author":"Harbour","year":"2013","journal-title":"Nat. Genet."},{"key":"2026081714194917200_cit8","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/path.4483","article-title":"Sf3b1 mutations\nconstitute a novel\ntherapeutic target in breast cancer","volume":"235","author":"Maguire","year":"2015","journal-title":"J. Pathol."},{"key":"2026081714194917200_cit9","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.1016\/0006-2952(94)90171-6","article-title":"Stability of peptide nucleic-acids\nin human serum and cellular-extracts","volume":"48","author":"Demidov","year":"1994","journal-title":"Biochem.\nPharmacol."},{"key":"2026081714194917200_cit10","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/365566a0","article-title":"Pna hybridizes to complementary oligonucleotides obeying\nthe watson-crick hydrogen-bonding rules","volume":"365","author":"Egholm","year":"1993","journal-title":"Nature"},{"key":"2026081714194917200_cit11","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1126\/science.1962210","article-title":"Sequence-selective\nrecognition of DNA by strand displacement with a thymine-substituted\npolyamide","volume":"254","author":"Nielsen","year":"1991","journal-title":"Science"},{"key":"2026081714194917200_cit12","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.chembiol.2003.09.014","article-title":"Recognition\nof chromosomal DNA by\npnas","volume":"11","author":"Kaihatsu","year":"2004","journal-title":"Chem. Biol."},{"key":"2026081714194917200_cit13","doi-asserted-by":"publisher","first-page":"3615","DOI":"10.1172\/JCI33483","article-title":"Chemical\nmodification: The key to clinical application of rna interference?","volume":"117","author":"Corey","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2026081714194917200_cit14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1089\/oli.2010.0266","article-title":"Efficiency of cellular\ndelivery of antisense peptide nucleic acid by electroporation depends\non charge and electroporation geometry","volume":"21","author":"Joergensen","year":"2011","journal-title":"Oligonucleotides"},{"key":"2026081714194917200_cit15","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/nprot.2006.92","article-title":"Enhanced delivery\nof cell-penetrating peptide\u2013peptide\nnucleic acid conjugates by endosomal disruption","volume":"1","author":"Shiraishi","year":"2006","journal-title":"Nat. Protoc."},{"key":"2026081714194917200_cit16","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/S1074-5521(99)80046-5","article-title":"Cellular delivery\nof peptide nucleic acids and inhibition of human telomerase","volume":"6","author":"Hamilton","year":"1999","journal-title":"Chem. Biol."},{"key":"2026081714194917200_cit17","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/S0169-409X(02)00182-5","article-title":"Cellular delivery of peptide nucleic\nacid (pna)","volume":"55","author":"Koppelhus","year":"2003","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026081714194917200_cit18","doi-asserted-by":"publisher","first-page":"10277","DOI":"10.1073\/pnas.89.21.10277","article-title":"Anthrax toxin protective\nantigen is activated by a cell-surface protease with the sequence\nspecificity and catalytic properties of furin","volume":"89","author":"Klimpel","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081714194917200_cit19","doi-asserted-by":"crossref","first-page":"20607","DOI":"10.1016\/S0021-9258(17)32036-7","article-title":"Anthrax\nprotective antigen forms oligomers during intoxication of mammalian-cells","volume":"269","author":"Milne","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2026081714194917200_cit20","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1016\/j.jmb.2009.07.037","article-title":"The protective antigen component of anthrax toxin forms\nfunctional octameric complexes","volume":"392","author":"Kintzer","year":"2009","journal-title":"J. Mol. Biol."},{"key":"2026081714194917200_cit21","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.jmb.2004.09.067","article-title":"Acid-induced unfolding of the amino-terminal\ndomains\nof the lethal and edema factors of anthrax toxin","volume":"344","author":"Krantz","year":"2004","journal-title":"J. Mol. Biol."},{"key":"2026081714194917200_cit22","doi-asserted-by":"publisher","first-page":"11944","DOI":"10.1038\/srep11944","article-title":"Translocation\nof non-canonical polypeptides into cells using protective antigen","volume":"5","author":"Rabideau","year":"2015","journal-title":"Sci. Rep."},{"key":"2026081714194917200_cit23","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1002\/cbic.201402290","article-title":"Delivery\nof antibody mimics into\nmammalian cells via anthrax toxin protective antigen","volume":"15","author":"Liao","year":"2014","journal-title":"ChemBioChem"},{"key":"2026081714194917200_cit24","doi-asserted-by":"publisher","first-page":"12531","DOI":"10.1073\/pnas.93.22.12531","article-title":"Anthrax toxin-mediated delivery of\na cytotoxic t-cell epitope in vivo","volume":"93","author":"Ballard","year":"1996","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"key":"2026081714194917200_cit25","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/nmeth862","article-title":"Imaging\nspecific cell-surface proteolytic activity in single living cells","volume":"3","author":"Hobson","year":"2006","journal-title":"Nat. Methods"},{"key":"2026081714194917200_cit26","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.bbrc.2008.08.124","article-title":"Effective delivery of antisense peptide\nnucleic acid oligomers into cells by anthrax protective antigen","volume":"376","author":"Wright","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026081714194917200_cit27","doi-asserted-by":"publisher","first-page":"10749","DOI":"10.1021\/ja302354v","article-title":"Protein\nthioester synthesis enabled by sortase","volume":"134","author":"Ling","year":"2012","journal-title":"J. Am.\nChem. Soc."},{"key":"2026081714194917200_cit28","doi-asserted-by":"publisher","first-page":"11399","DOI":"10.1073\/pnas.1101046108","article-title":"A general\nstrategy for the evolution\nof bond-forming enzymes using yeast display","volume":"108","author":"Chen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081714194917200_cit29","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/S0021-9258(19)77000-8","article-title":"Structure and activity\nof diphtheria toxin. 1. Thiol-dependent\ndissociation of fraction of toxin into enzymically active and inactive\nfragments","volume":"246","author":"Collier","year":"1971","journal-title":"J. Biol. Chem."},{"key":"2026081714194917200_cit30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/978-3-642-76966-5_2","article-title":"Diphtheria-toxin and pseudomonas-aeruginosa\nexotoxin-a\n- active-site structure and enzymatic mechanism","volume":"175","author":"Wilson","year":"1992","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2026081714194917200_cit31","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1126\/science.1113380","article-title":"A phenylalanine\nclamp catalyzes protein translocation through the anthrax toxin pore","volume":"309","author":"Krantz","year":"2005","journal-title":"Science"},{"key":"2026081714194917200_cit32","doi-asserted-by":"publisher","first-page":"4346","DOI":"10.1073\/pnas.0800701105","article-title":"Phenylalanine-427\nof anthrax protective antigen functions in both pore formation and\nprotein translocation","volume":"105","author":"Sun","year":"2008","journal-title":"Proc. Natl. Acad. Sci.\nU. S. A."},{"key":"2026081714194917200_cit33","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1083\/jcb.111.3.807","article-title":"Nuclear-protein import in permeabilized\nmammalian-cells requires soluble cytoplasmic factors","volume":"111","author":"Adam","year":"1990","journal-title":"J. Cell Biol."},{"key":"2026081714194917200_cit34","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nchembio.2007.18","article-title":"Spliceostatin a targets sf3b and inhibits both splicing\nand nuclear retention of pre-mrna","volume":"3","author":"Kaida","year":"2007","journal-title":"Nat. Chem.\nBiol."},{"key":"2026081714194917200_cit35","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/S1046-2023(02)00023-3","article-title":"Analysis of gene function\nin somatic mammalian cells using small interfering rnas","volume":"26","author":"Elbashir","year":"2002","journal-title":"Methods"},{"key":"2026081714194917200_cit36","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1021\/bi0020630","article-title":"Inhibition\nof gene\nexpression inside cells by peptide nucleic acids: Effect of mrna target\nsequence, mismatched bases, and pna length","volume":"40","author":"Doyle","year":"2001","journal-title":"Biochemistry"},{"key":"2026081714194917200_cit37","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.molonc.2012.12.003","article-title":"Targeting her2-positive\ncancer cells with receptor-redirected anthrax protective antigen","volume":"7","author":"Mccluskey","year":"2013","journal-title":"Mol. Oncol."},{"key":"2026081714194917200_cit38","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/nrc1122","article-title":"Occurrence of leukaemia\nfollowing\ngene therapy of x-linked scid","volume":"3","author":"Kohn","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"2026081714194917200_cit39","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1021\/bc050283q","article-title":"Evaluation\nof cell-penetrating peptides (cpps) as vehicles\nfor intracellular delivery of antisense peptide nucleic acid (pna)","volume":"17","author":"Bendifallah","year":"2006","journal-title":"Bioconjugate Chem."},{"key":"2026081714194917200_cit40","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1056\/NEJMoa1103283","article-title":"Somatic sf3b1 mutation in myelodysplasia\nwith ring sideroblasts","volume":"365","author":"Papaemmanuil","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"2026081714194917200_cit41","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent pathway\nmutations of splicing machinery in myelodysplasia","volume":"478","author":"Yoshida","year":"2011","journal-title":"Nature"},{"key":"2026081714194917200_cit42","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nature11143","article-title":"Whole-genome analysis\ninforms breast cancer response to aromatase inhibition","volume":"486","author":"Ellis","year":"2012","journal-title":"Nature"},{"key":"2026081714194917200_cit43","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/ng.2523","article-title":"Recurrent mutations at codon 625 of the splicing factor\nsf3b1 in uveal melanoma","volume":"45","author":"Harbour","year":"2013","journal-title":"Nat. Genet."},{"key":"2026081714194917200_cit44","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/j.cell.2012.08.029","article-title":"Mapping the\nhallmarks of lung adenocarcinoma with massively parallel sequencing","volume":"150","author":"Imielinski","year":"2012","journal-title":"Cell"},{"key":"2026081714194917200_cit45","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.ccell.2016.08.006","article-title":"Physiologic expression of sf3b1\u00ad(k700e)\ncauses impaired erythropoiesis, aberrant splicing, and sensitivity\nto therapeutic spliceosome modulation","volume":"30","author":"Obeng","year":"2016","journal-title":"Cancer\nCell"},{"key":"2026081714194917200_cit46","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1038\/nm.4165","article-title":"Therapeutic\ntargeting of splicing in cancer","volume":"22","author":"Lee","year":"2016","journal-title":"Nat. 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Acad. Sci. U. S. A."},{"key":"2026081714194917200_cit51","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nrmicro2147","article-title":"Coronaviruses post-sars: Update on replication and\npathogenesis","volume":"7","author":"Perlman","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"2026081714194917200_cit52","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1097\/01.qco.0000244043.08264.fc","article-title":"Infectious\ndiseases emerging from\nchinese wet-markets: Zoonotic origins of severe respiratory viral\ninfections","volume":"19","author":"Woo","year":"2006","journal-title":"Curr. Opin. Infect. Dis."},{"key":"2026081714194917200_cit53","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nrm2777","article-title":"Mechanisms of alternative\nsplicing regulation: Insights\nfrom molecular and genomics approaches","volume":"10","author":"Chen","year":"2009","journal-title":"Nat.\nRev. Mol. 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