New publication from Ragon Institute and Brigham and Women’s Hospital researchers use Tapestri®’s unique single-cell DNA and multi-omics capabilities to identify surface marker signatures in latent HIV reservoirs that could lead to new treatment approaches
SOUTH SAN FRANCISCO, Jan. 5, 2023 – Mission Bio, the pioneer in high-throughput single-cell DNA and multi-omics analysis, announced a new publication in Nature from researchers at the Ragon Institute of MGH, MIT, and Harvard and Brigham and Women’s Hospital using Mission Bio’s Tapestri® Platform to identify phenotypic signatures of hidden human immunodeficiency virus 1 (HIV-1)-infected immune cells that allow the virus to evade immune response. The team utilized Tapestri®’s proteogenomics capabilities to detect HIV DNA and corresponding surface markers on patients’ memory CD4+ T cells for the first time, as well as to develop a fingerprint for latent infection that may guide new treatment approaches.
HIV remains incurable because HIV-infected reservoir cells persist despite antiretroviral medications for patients’ entire lives. Previous research has suggested that host immune cells can slowly deplete these reservoir cells, lending hope to the idea that immunotherapy approaches could someday be used to treat disease. But scientists have long been stymied in efforts to adequately profile the surface phenotype of these cells, to understand their vulnerabilities and identify molecular targets for immunotherapeutic interventions.
In the new paper, the Boston-based teams used single-cell proteogenomic profiling on the Tapestri® Platform to simultaneously evaluate HIV DNA and the phenotype of single unmanipulated, patient-derived cells. Cells were stained with 53 surface antibodies, while HIV DNA segments were amplified simultaneously using 18 defined primer sets spanning strategic positions in the HIV genome. Using high-throughput DNA + multi-omics, the researchers identified phenotypic signatures of HIV reservoir cells, likely driven by host immune activity. The findings could lead to clinical strategies that reduce long-term HIV persistence.
“High-throughput, single-cell sequencing now allows us to take a precise look at the surface profile of the very small numbers of infected cells that persist lifelong despite antiretroviral therapy, and can fuel rebound viremia when treatment is stopped,” said Mathias Lichterfeld, MD, PhD, professor of Medicine at Harvard Medical School, infectious disease physician at the Brigham and Women’s Hospital and Massachusetts General Hospital, and senior author of the study. “With this knowledge, we are able to understand their susceptibilities and vulnerabilities, and can develop a tailored immune response to target these cells.”
“Over more than four decades, HIV has slowly but progressively revealed its secrets, and this is yet another critical secret revealed. The ability to visualize individual reservoir cells was a pipe dream, and now has become a reality,” says Bruce Walker, MD, Director of the Ragon Institute of MGH, MIT and Harvard and co-investigator in the study. “Now we must build on this information to eradicate these cells.”
“This new paper demonstrates the versatility of the Tapestri® Platform,” said Todd Druley, MD, PhD, Chief Medical Officer of Mission Bio. “While most researchers associate Tapestri® with its remarkable clinical impact in the hematological oncology and solid tumor fields, the platform is a powerful tool for correlating DNA and immunophenotype at the single-cell level across disciplines – ranging from HIV research to gene and cell therapy clinical quality attribute measurement.”
The paper, “Phenotypic signatures of immune selection in HIV-1 reservoir cells,” published on January 4 in Nature.
To learn more about Mission Bio and the Tapestri® Platform, please visit www.missionbio.com.
About Mission Bio
Mission Bio is a life sciences company that accelerates discoveries and cures for a wide range of diseases by equipping researchers with the tools they need to better measure and predict our resistance and response to new therapies. Mission Bio’s multi-omics approach improves time-to-market for new therapeutics, including innovative cell and gene therapies that provide new pathways to health. Founded in 2014, Mission Bio has secured investment from Novo Growth, Cota Capital, Agilent Technologies, Mayfield Fund, and others.
The company’s Tapestri® Platform gives researchers around the globe the power to interrogate every molecule in a cell together, providing a comprehensive understanding of activity from a single sample. Tapestri® is the only commercialized multi-omics platform capable of analyzing DNA and protein simultaneously from the same sample at single-cell resolution. The Tapestri® Platform is being utilized by customers at leading research centers, pharmaceutical, and diagnostics companies worldwide to develop treatments and eventually cures for cancer.