 | The Long History of Rapid Vaccine Development
In the 1970s, Phillip Sharp and his colleagues on the fifth floor of the MIT Center for Cancer Research set out to unravel the mysteries of tumor virology, cancer genetics, and cell biology. Looking at parts of the adenovirus genome responsible for tumor development, Sharp had long wondered why RNA in the nucleus was longer than RNA found outside the nucleus in the cytoplasm. While this curiosity led to the Nobel Prize-winning discovery of split genes and spliced RNA, neither Sharp nor his colleagues were thinking about the possibility of mRNA vaccines at the time. Nevertheless, that discovery, together with many years of mRNA research and key technology advances like nanoparticle delivery of RNA, set the stage for companies such as Pfizer and Moderna to develop mRNA-based COVID-19 vaccines with record speed.
The discoveries that enabled RNA vaccines | RNA vaccines explained |
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Small Molecule, Big Potential
A multidisciplinary team from the Koehler Lab identified a compound that could target key proteins in advanced prostate cancer, as well as a variety of other cancer types. The compound, KI-ARv-03, works by selectively binding to an androgen receptor cofactor known as CDK9, thereby destabilizing androgen receptor proteins in a key pathway contributing to the development of castration-resistant prostate cancer (CRPC) and curbing the expression of associated oncogenes. The study appears in Cell Chemical Biology and was supported in part by the Koch Institute-Dana-Farber/Harvard Cancer Center Bridge Project, the MIT Center for Precision Cancer Medicine, and Janssen Pharmaceuticals, Inc., via the Transcend partnership.
Kronos Bio, co-founded by Koehler, has developed a more powerful version of the CDK9 inhibitor, KB-0742 and recently received IND clearance to begin a Phase 1/2 clinical trial in 2021. Preclinical tests in cell lines and mouse models revealed significantly reduced tumor growth in CRPC models and other oncogene-addicted cancers. |
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Bringing Computers Into the Protein Fold
The Keating Lab mixes lab work, modeling and, most recently, machine learning to understand how protein sequences determine their interactions. While the COVID-19 crisis disrupts lab research, Keating’s team is focusing on computational projects, including exploring interactions between “short linear motifs” and a family of proteins implicated in metastasis. |
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Conducting Research in a New Way
A new imaging technique from the Boyden Lab, published in Cell, identifies up to five different molecule types from random, distinct locations throughout a cell, uncovering a full “symphony” of cellular activity. The technology will be instrumental in understanding how cell signaling differs between cells from healthy and diseased tissue. |
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Blazing Trails in Biopharma
Dragonfly Therapeutics Head of Biology Ann Cheung is featured among Endpoints News’ top trailblazers in biopharmaceutical research & development. The profile chronicles her career transitions from her early years as the lone immuno-oncology researcher in the Jacks Lab to her current role moving NK cell therapies from bench to bedside. Longtime Koch Institute member Aviv Regev is also recognized for her groundbreaking work in single cell sequencing, computational biology, and genetics. |
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Division of Liver
The Shalek Lab codiscovered a mechanism that helps damaged livers function while they regenerate. A study appearing in Nature Communications showed that liver cells increase transcription of important genes ahead of proliferation, and may even divide labor between cells that proliferate and those that maintain core functions. This contributes to a larger effort to identify stem cells in normal and cancerous liver tissue, and is funded in part by the MIT Stem Cell Initiative. |
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Green Light for KI Faculty Startups
The end of year brings new beginnings for KI faculty startups. Lumicell’s signature imaging system has been granted fast track designation approval for breast cancer treatment. Fate Therapeutics reports positive Phase 1 data for its combination immunotherapy as well as a promising case study for its targeted NK cell therapy, both in lymphoma patients. Verastem announces Phase 2 initiation for trials in recurrent low-grade serous ovarian cancer. Syros presents positive results from Phase 2 trials in acute myeloid leukemia and an initiation plan for future trials. Finally, Dragonfly Therapeutics has licensed its first NK cell based immunotherapy candidate to Merck. |
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