{"676545":{"#nid":"676545","#data":{"type":"news","title":"mRNA and Gene Editing Tools Offer New Hope for Dengue Virus Treatment","body":[{"value":"\u003Cp\u003EDengue virus, a painful and sometimes fatal mosquito-borne infection well known in tropical countries, is surging rapidly across the planet. Now, 4 billion people live in places \u2014 like the southeastern United States \u2014 at risk for the disease, which doesn\u2019t have an effective antiviral treatment. Yet.\u003C\/p\u003E\u003Cp\u003EA team of researchers led by biomedical engineer\u0026nbsp;\u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/faculty\/Philip-Santangelo\u0022\u003EPhil Santangelo\u003C\/a\u003E has developed a breakthrough therapy to target and kill the virus using the gene editing tool CRISPR-Cas13. The team\u2019s systemic delivery of the treatment was successful in treating dengue virus in mice, as\u0026nbsp;\u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41564-024-01726-6\u0022\u003Ethe researchers explained in \u003Cem\u003ENature Microbiology\u003C\/em\u003E\u003C\/a\u003E.\u003C\/p\u003E\u003Cp\u003EDengue is difficult to treat in part because there are four different serotypes of the virus, which means four different targets for a vaccine. People infected with one serotype who then contract a second version of the virus can end up with a serious disease. That second attack can end up amplifying the first. Symptoms include fever, nausea, rash, aches and pains (including behind the eyes), and in some cases, internal bleeding, shock, and death.\u003C\/p\u003E\u003Cp\u003E\u201cThere are several challenges with trying to treat dengue, so we wondered, is it possible for us to produce an mRNA-based, CRISPR-based antiviral where one shot can clear the virus,\u201d said Santangelo, professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. \u201cAnd that\u2019s basically what we\u2019ve shown.\u201d\u0026nbsp;\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003ENew Use for the Tech\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EWith the global proliferation of the Aedes mosquito that spreads dengue and other viruses, the timing of such a treatment would be fortuitous.\u003C\/p\u003E\u003Cp\u003E\u201cUnfortunately, climate change is enabling an increase of these virus-causing mosquitos,\u201d said Santangelo, also a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech. \u201cSo, it\u2019s a good idea to be prepared.\u201d\u003C\/p\u003E\u003Cp\u003EThis is the first time an mRNA-based CRISPR treatment has worked against systemic viral infections in animal models. But Santangelo demonstrated its efficacy in earlier studies focused on lung diseases, including a\u0026nbsp;\u003Ca href=\u0022https:\/\/research.gatech.edu\/healing-breath-researchers-dramatically-improve-inhalable-mrna-therapy\u0022\u003Etreatment for coronavirus\u003C\/a\u003E. That was an inhalable treatment using polymeric nanoparticles \u2014 large, biodegradable molecules ideal for delivering medicine directly to the lungs.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EFor the dengue virus study, the team used lipid nanoparticles (LNPs), which are like tiny fat bubbles that transport drugs through the bloodstream and into cells. The nanoparticles carried a custom-coded messenger RNA (mRNA) molecule.\u003C\/p\u003E\u003Cp\u003EThe mRNA was encoded with Cas13a (a CRISPR protein that can cut viral RNA) and guide RNAs (to direct the Cas13a to the viral RNA that needs to be cut). The process basically created a set of instructions. When the encoded mRNA is delivered to infected cells via the LNPs, the cell uses those instructions to build Cas13a and guide RNAs, which degrade the viral RNA within those targeted cells.\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003EMilitary Precision\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EA single dose of the treatment was given to mice infected with lethal doses of two serotypes of dengue virus, DENV-2 and DENV-3. All the treated mice survived with no unintended damage to their RNA. Following treatment, the researchers also looked for evidence of the virus in the mice\u2019s brains but couldn\u2019t find any.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u201cIt looks like our treatment precludes the virus from getting into the brain,\u201d Santangelo said. \u201cThis may not be super critical for dengue, which doesn\u2019t end up in the human brain. But this discovery could be really important for Zika virus, Japanese encephalitis, West Nile, and other viruses that do affect the human brain.\u201d\u003C\/p\u003E\u003Cp\u003EThe study was funded by the Defense Advanced Research Projects Agency (DARPA), which is interested in protecting soldiers from mosquito-borne illnesses. Santangelo\u2019s team now is testing their approach on dengue\u2019s other serotypes and will study the treatment in other viruses.\u003C\/p\u003E\u003Cp\u003E\u201cWe\u2019re very interested in trying these kinds of approaches to go after as many viruses as we can with one, potent treatment,\u201d said Santangelo, whose team included researchers from Georgia State University as well as Emory\u2019s Computational Core. \u201cWe\u2019re trying to find the most efficient way to kill these viruses. We\u2019re not quite there yet, but we\u2019re going to get there eventually.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION:\u003C\/strong\u003E Basu, M., Zurla, C., Auroni, T.T. \u003Cem\u003Eet al.\u003C\/em\u003E mRNA-encoded Cas13 can be used to treat dengue infections in mice. \u003Cem\u003ENat Microbiol\u003C\/em\u003E \u003Cstrong\u003E9\u003C\/strong\u003E, 2160\u20132172 (2024). \u003Ca href=\u0022https:\/\/doi.org\/10.1038\/s41564-024-01726-6\u0022\u003Ehttps:\/\/doi.org\/10.1038\/s41564-024-01726-6\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis research was supported by the Defense Advanced Research Projects Agency, grant No. HR0011-19-2-0008. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of any funding agency.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E","summary":"","format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EPhil Santangelo has developed a treatment for dengue virus using mRNA and CRISPR technology. It could also work for other mosquito-borne viruses.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Phil Santangelo has developed a treatment for dengue virus using mRNA and CRISPR technology."}],"uid":"28153","created_gmt":"2024-09-05 15:56:30","changed_gmt":"2024-09-12 16:33:26","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2024-09-05T00:00:00-04:00","iso_date":"2024-09-05T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"674832":{"id":"674832","type":"image","title":"Phil Santangelo","body":"\u003Cp\u003EPhil Santangelo has led development of a new treatment for dengue virus, using mRNA and CRISPR technology. \u0026nbsp;\u2014 Photo by Jack Kearse\u003C\/p\u003E","created":"1725551522","gmt_created":"2024-09-05 15:52:02","changed":"1725551669","gmt_changed":"2024-09-05 15:54:29","alt":"Phil Santangelo, faculty member of the Petit Institute for Bioengineering and Bioscience, has led development of a new treatment for dengue virus, using mRNA and CRISPR technology.","file":{"fid":"258396","name":"M110701-23JK-058 Final06.jpg","image_path":"\/sites\/default\/files\/2024\/09\/05\/M110701-23JK-058%20Final06.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/09\/05\/M110701-23JK-058%20Final06.jpg","mime":"image\/jpeg","size":1746442,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/09\/05\/M110701-23JK-058%20Final06.jpg?itok=uiPzaROU"}}},"media_ids":["674832"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"}],"keywords":[{"id":"6718","name":"Phil Santangelo"},{"id":"187423","name":"go-bio"},{"id":"193939","name":"Dengue"},{"id":"191727","name":"mRNA therapies"},{"id":"985","name":"mRNA"},{"id":"170522","name":"CRISPR"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJerry Grillo\u003C\/p\u003E","format":"limited_html"}],"email":["Jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}