{"679023":{"#nid":"679023","#data":{"type":"news","title":"Special Delivery Nanoparticle Sidesteps the \u2018Middlemen\u2019","body":[{"value":"\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003EMiddlemen get a bad rap for adding cost and complications to an operation. So, eliminating the go-betweens can reduce expense and simplify a process, increasing efficiency and consumer happiness.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/faculty\/James-Dahlman\u0022\u003EJames Dahlman\u003C\/a\u003E and his research team have been thinking along those same lines for stem cell treatments. They\u2019ve created a technique that eliminates noisome middlemen and could lead to new, less-invasive treatments for blood disorders and genetic diseases. It sidesteps the discomfort and risks of current treatments, making life easier for patients.\u003C\/p\u003E\u003Cp\u003E\u201cThis would be an alternative to invasive hematopoietic stem cell therapies \u2014 we could just give you an IV drip,\u201d said Dahlman, McCamish Early Career Professor in the Wallace H. Coulter Department of Biomedical Engineering. \u201cIt simplifies the process and reduces the risks to patients. That\u2019s why this work is important.\u201d\u003C\/p\u003E\u003Cp\u003EDahlman and a team of investigators from Georgia Tech, Emory University, and the University of California, Davis, \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41587-024-02470-2\u0022\u003Epublished their approach in the journal \u003Cem\u003ENature Biotechnology\u003C\/em\u003E\u003C\/a\u003E.\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003EMinding the Parents\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EHematopoietic stem cells (HSCs) are like parent cells. Residing in the bone marrow, they produce all types of cells needed to sustain the blood and immune systems. Their versatility makes HSCs a valuable therapeutic tool in treating genetic blood diseases, such as sickle cell anemia, immune deficiencies, and some cancers.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EHSC therapies usually involve extracting cells from the patient\u2019s bone marrow and re-engineering them in a lab. Meanwhile, the patient endures chemotherapy to help prepare their body to receive the modified HSCs.\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cdiv\u003E\u003Cp\u003E\u201cThese therapies are effective but also hard on the patients,\u201d Dahlman said. \u201cPatients undergo chemotherapy to wipe out their immune systems so the body will accept the therapeutic cells without a fight. The procedure can be life-threatening. We\u2019re hoping to change that.\u201d\u003C\/p\u003E\u003Cp\u003EHSCs can also be modified directly inside the body. The procedure uses lipid nanoparticles (LNPs) to carry genetic instructions to the stem cells. The LNPs have targeting ligands attached \u2014 molecules designed to find specific target cells. Precisely engineering them adds layers of time, complexity, and cost to the process. They are, like extraction from bone marrow and chemotherapy, another middleman.\u003C\/p\u003E\u003Cp\u003EThe researchers wanted something simpler. They found it in a specific nanoparticle called LNP67.\u003C\/p\u003E\u003Cp\u003E\u201cUnlike other nanoparticle designs, this one doesn\u2019t require a targeting ligand,\u201d Dahlman said. \u201cIt\u2019s chemically simple, which means it\u2019s easier to manufacture and opens the door to eventually scaling production, like mRNA vaccines.\u201d\u003C\/p\u003E\u003Ch4\u003E\u003Cstrong\u003EOvercoming the Liver\u003C\/strong\u003E\u003C\/h4\u003E\u003Cp\u003EThe key to LNP67\u2019s success is its ability to dodge the liver, the body\u2019s primary blood filter. Foreign invaders, even helpful invaders delivered through an IV as medicine, can be captured by a healthy liver.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u201cThe liver absorbs almost everything,\u201d Dahlman said. \u201cBut, by reducing what it captures by even as little as 10 percent, we can double delivery to other tissues where the nanoparticles and their payloads are needed.\u201d\u003C\/p\u003E\u003Cp\u003EThe researchers developed 128 unique nanoparticles, narrowing the list down to 105 LNPs that didn\u2019t have targeting ligands. These were ultimately screened and evaluated for their performance in delivering genetic instructions (in the form of mRNA) effectively and safely.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ELNP67 emerged as the best performer thanks to its stealthy design. For example, the surface is designed to repel proteins and other molecules that would mark the LNP for capture by the liver. This feature helped the particles circulate more evenly in the body and reach the HSCs.\u003C\/p\u003E\u003Cp\u003E\u201cWe achieved low-dose delivery without a target ligand, which is exciting,\u201d Dahlman said. \u201cThis is something we\u2019ve been working toward for years, and I\u2019m very happy we got there.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECitation:\u003C\/strong\u003E Hyejin Kim, Ryan Zenhausern, Kara Gentry, Liming Lian, Sebastian G. Huayamares, Afsane Radmand, David Loughrey, Ananda Podilapu, Marine Z. C. Hatit, Huanzhen Ni, Andrea Li, Aram Shajii, Hannah E. Peck, Keyi Han, Xuanwen Hua, Shu Jia, Michele Martinez, Charles Lee, Philip J. Santangelo, Alice Tarantal, James E. Dahlman. \u003Ca href=\u0022https:\/\/www.nature.com\/articles\/s41587-024-02470-2\u0022\u003ELipid Nanoparticle Study, Nov. 2024\u003C\/a\u003E, \u003Cem\u003ENature Biotechnology.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFunding:\u003C\/strong\u003E This research was supported by the National Institutes of Health grants UL1TR002378, UH3-TR002855, U42 OD027094, and TL1DK136047; National Science Foundation grant 0923395. 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\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECompeting Interests:\u003C\/strong\u003E James Dahlman, Marine Z. C. Hatit, and Huanzhen Ni have filed a provisional patent related to this manuscript (US patent application number 63\/632,354).\u0026nbsp;\u003C\/p\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E","summary":"","format":"limited_html"}],"field_subtitle":[{"value":"Researchers demonstrate stem cell treatment without chemotherapy and painful bone marrow procedure"}],"field_summary":[{"value":"\u003Cp\u003EResearchers develop a lipid nanoparticle that can program stem cells while inside the body, avoiding the need for chemotherapy and bone marrow extraction in stem cell treatments.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers develop nanoparticle that can program stem cells while inside the body, avoiding the need for chemotherapy and bone marrow extraction in stem cell treatments."}],"uid":"28153","created_gmt":"2024-12-21 12:43:16","changed_gmt":"2024-12-21 13:02:54","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","location":"Atlanta, GA","dateline":{"date":"2024-12-21T00:00:00-05:00","iso_date":"2024-12-21T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"675906":{"id":"675906","type":"image","title":"Lipid nanoparticle","body":"\u003Cp\u003ELipid nanoparticles in their element: This computer generated image shows lipid nanoparticles, which are used to transport payloads to targets inside the body.\u0026nbsp;\u003C\/p\u003E","created":"1734785517","gmt_created":"2024-12-21 12:51:57","changed":"1734785634","gmt_changed":"2024-12-21 12:53:54","alt":"Lipid nanoparticle AI generated image from adobe stock","file":{"fid":"259580","name":"Screen Shot 2024-12-17 at 12.14.01 PM.png","image_path":"\/sites\/default\/files\/2024\/12\/21\/Screen%20Shot%202024-12-17%20at%2012.14.01%20PM.png","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/2024\/12\/21\/Screen%20Shot%202024-12-17%20at%2012.14.01%20PM.png","mime":"image\/png","size":9829642,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/2024\/12\/21\/Screen%20Shot%202024-12-17%20at%2012.14.01%20PM.png?itok=g8m6iQ-v"}}},"media_ids":["675906"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"},{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"138","name":"Biotechnology, Health, Bioengineering, Genetics"},{"id":"140","name":"Cancer Research"},{"id":"145","name":"Engineering"},{"id":"146","name":"Life Sciences and Biology"},{"id":"149","name":"Nanotechnology and Nanoscience"},{"id":"135","name":"Research"}],"keywords":[{"id":"189917","name":"lipid nanoparticles"},{"id":"186748","name":"lipid nanoparticle"},{"id":"169030","name":"stem cell treatment"},{"id":"171013","name":"stem cell therapy"},{"id":"187915","name":"go-researchnews"},{"id":"187423","name":"go-bio"},{"id":"182868","name":"blood cells"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"},{"id":"71881","name":"Science and Technology"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022mailto:jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}