Nanotechnology for Targeted in vivo Gene Editing
Event details
| Date | 09.09.2014 |
| Hour | 14:15 |
| Speaker | James E. Dahlman, PhD, Broad Institute (MIT/Harvard), and MIT Koch Institute for Cancer Research, Cambridge, MA (USA) |
| Location | |
| Category | Conferences - Seminars |
JOINT MATERIALS SCIENCE and BIOENGINEERING SEMINAR
Abstract:
Once viewed as a passive link between DNA and protein, RNAs are now known to actively and precisely modify gene expression. For example, siRNAs can reduce the expression of any protein, while CRISPR-Cas9 enables scientists to make targeted and permanent changes in genomic DNA for the first time.
Because RNAs can, in theory, be used to easily manipulate many genes simultaneously, they could revolutionize the way we study and treat disease. However, the full scientific and clinical potential of RNA is currently limited, because we can not deliver RNA to the right cells in vivo. In vivo RNA delivery is difficult; the molecule must be (a) protected from degradation in the bloodstream, (b) delivered to the correct target tissue, and (c) ferried into the right cell, without setting off an unwanted immune response. While nanoparticles have delivered RNA to the liver, delivery to other cell types has remained difficult.
Herein, I will describe new tools for in vivo RNA delivery and gene editing, developed by integrating chemical engineering, nanotechnology, biology, and genomics. One tool, a nanoparticle named 7C1, has delivered RNA to the heart and lung at very low doses, has delivered 5 different RNAs concurrently, has been used by 10 labs across the United States to study inflammation, cancer, heart disease, and lung disease, and is under evaluation for clinical trials in lung cancer and heart disease. Surprisingly, unlike many other nanoparticles, 7C1 nanoparticles do not readily transfect hepatocytes or immune cells in vivo. We believe that this new tool, which has been described on the cover of Nature Nanotechnology and PNAS, can be used to easily make targeted changes in gene expression.
I will also describe our recent efforts to generate in vivo DNA deletions using the CRISPR-Cas9 system.
Bio:
James Dahlman is a post-doctoral fellow whose research lies at the interface of engineering, nanotechnology, and medicine. He received his PhD from the MIT/Harvard Medical School HST program, where he studied targeted drug delivery with Robert Langer. At the end of his PhD, James had seventeen papers published, or in various stages of preparation, including first author papers in PNAS, Nature Reviews Cancer, and a cover feature in Nature Nanotechnology. His technology, which preferentially targets drugs to the lung and heart, has been used by ten labs across the United States to study cancer, atherosclerosis, inflammation, emphysema, and pulmonary hypertension, and is being evaluated for clinical trials in lung cancer and cardiovascular disease. More recently, James invented a platform that will enable scientists to study thousands of clinical drug delivery vehicles in vivo (currently, only a few candidates are normally tested in vivo). He is currently studying in vivo genome editing using CRISPR-Cas9 with Feng Zhang at the Broad Institute; his research will combine genomics, drug delivery, nanotechnology, and RNA, with the goal of radically improving the way we study gene function.
James has given nearly thirty presentations, including invited talks at Harvard and in Europe, has received numerous awards for his work as a PhD student, and was likely the only student in the United States to simultaneously win the NSF, NDSEG, MIT Presidential, Whitaker, and NIH Oxford Cambridge Fellowships in 2009.
Abstract:
Once viewed as a passive link between DNA and protein, RNAs are now known to actively and precisely modify gene expression. For example, siRNAs can reduce the expression of any protein, while CRISPR-Cas9 enables scientists to make targeted and permanent changes in genomic DNA for the first time.
Because RNAs can, in theory, be used to easily manipulate many genes simultaneously, they could revolutionize the way we study and treat disease. However, the full scientific and clinical potential of RNA is currently limited, because we can not deliver RNA to the right cells in vivo. In vivo RNA delivery is difficult; the molecule must be (a) protected from degradation in the bloodstream, (b) delivered to the correct target tissue, and (c) ferried into the right cell, without setting off an unwanted immune response. While nanoparticles have delivered RNA to the liver, delivery to other cell types has remained difficult.
Herein, I will describe new tools for in vivo RNA delivery and gene editing, developed by integrating chemical engineering, nanotechnology, biology, and genomics. One tool, a nanoparticle named 7C1, has delivered RNA to the heart and lung at very low doses, has delivered 5 different RNAs concurrently, has been used by 10 labs across the United States to study inflammation, cancer, heart disease, and lung disease, and is under evaluation for clinical trials in lung cancer and heart disease. Surprisingly, unlike many other nanoparticles, 7C1 nanoparticles do not readily transfect hepatocytes or immune cells in vivo. We believe that this new tool, which has been described on the cover of Nature Nanotechnology and PNAS, can be used to easily make targeted changes in gene expression.
I will also describe our recent efforts to generate in vivo DNA deletions using the CRISPR-Cas9 system.
Bio:
James Dahlman is a post-doctoral fellow whose research lies at the interface of engineering, nanotechnology, and medicine. He received his PhD from the MIT/Harvard Medical School HST program, where he studied targeted drug delivery with Robert Langer. At the end of his PhD, James had seventeen papers published, or in various stages of preparation, including first author papers in PNAS, Nature Reviews Cancer, and a cover feature in Nature Nanotechnology. His technology, which preferentially targets drugs to the lung and heart, has been used by ten labs across the United States to study cancer, atherosclerosis, inflammation, emphysema, and pulmonary hypertension, and is being evaluated for clinical trials in lung cancer and cardiovascular disease. More recently, James invented a platform that will enable scientists to study thousands of clinical drug delivery vehicles in vivo (currently, only a few candidates are normally tested in vivo). He is currently studying in vivo genome editing using CRISPR-Cas9 with Feng Zhang at the Broad Institute; his research will combine genomics, drug delivery, nanotechnology, and RNA, with the goal of radically improving the way we study gene function.
James has given nearly thirty presentations, including invited talks at Harvard and in Europe, has received numerous awards for his work as a PhD student, and was likely the only student in the United States to simultaneously win the NSF, NDSEG, MIT Presidential, Whitaker, and NIH Oxford Cambridge Fellowships in 2009.
Practical information
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