打开APP

你知道光遗传技术能用到细胞治疗吗?

  1. 细胞治疗

来源:本站原创 2018-03-16 14:26

生物谷将于2018年5月17-19日在上海举办2018(第九届)细胞治疗国际研讨会,本次会议有幸邀请到美国怀俄明大学Mark Gomelsky教授过来演讲,演讲题目:Developing cell therapies using near-infrared light optogenetics.以下是Mark Gomelsky教授的专访。个人简介:Dr. Mark Gomelsky is one


生物谷将于2018年5月17-19日在上海举办2018(第九届)细胞治疗国际研讨会,本次会议有幸邀请到美国怀俄明大学Mark Gomelsky教授过来演讲,演讲题目:Developing cell therapies using near-infrared light optogenetics.

以下是Mark Gomelsky教授的专访。


个人简介:Dr. Mark Gomelsky is one of the leaders in engineering synthetic, near-infrared light-activated optogenetic circuits to controll human cells in deep tissues. He is a Professor of Molecular Biology at the University of Wyoming and Founder of Eos LABS LLC, a startup company that developes light-activated engineered cells for therapeutic applications. Dr. Gomelsky has been elected as a Fellow of the American Association for the Advancement of Science (AAAS) for discoveries of light-controlled bacterial signal transduction pathways, and for fundamental work on the role of the second messenger cyclic di-GMP in controlling bacterial pathogenesis. He has published >80 articles and is frequently invited as a speaker at international conferences.. Dr. Gomelsky holds Ph.D. in Biological Sciences from Institute of Genetics and Selection of Industrial Microorganisms (Moscow, Russia). Before joining the faculty of the University of Wyoming (1999), he did his postdoctoral studies at Institut Pasteur (Paris, France) and the University of Texas Medical School (Houston, USA). He was Visiting Professor at Max Planck Institute for Medical Research (Heidelberg, Germany; 2007) and Karolinska Institute (Stockholm, Sweden; 2015).
 
Selected Publications:
 
First and Corresponding Author:

 
Gomelsky M. Photoactivated cells link diagnosis and therapy. Sci Transl Med. 2017 Apr 26;9(387). pii: eaan3936. doi: 10.1126/scitranslmed.aan3936.    ( IF 16.796 )
 
Römling U, Galperin MY, Gomelsky M. Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev. 2013 Mar;77(1):1-52. doi: 10.1128/MMBR.00043-12.    ( IF 14.533 )
 
Gomelsky M, Galperin MY. Bacterial second messengers, cGMP and c-di-GMP, in a quest for regulatory dominance. EMBO J. 2013 Sep 11;32(18):2421-3. doi: 10.1038/emboj.2013.193. Epub 2013 Aug 20.    ( IF 9.792 )
 
Ryu MH, Kang IH, Nelson MD, Jensen TM, Lyuksyutova AI, Siltberg-Liberles J, Raizen DM, Gomelsky M. Engineering adenylate cyclases regulated by near-infrared window light. Proc Natl Acad Sci U S A. 2014 Jul 15;111(28):10167-72. doi: 10.1073/pnas.1324301111. Epub 2014 Jun 30.    ( IF 9.661 )
 
Chen LH, K철seo휓lu VK, G체vener ZT, Myers-Morales T, Reed JM, D'Orazio SE, Miller KW, Gomelsky M. Cyclic di-GMP-dependent signaling pathways in the pathogenic Firmicute Listeria monocytogenes. PLoS Pathog. 2014 Aug 7;10(8):e1004301. doi: 10.1371/journal.ppat.1004301. eCollection 2014 Aug.    ( IF 6.608 )
Others:
2013    1 in MBio    ( IF 6.956 )
2012    1 in Plos Pathog    ( IF 6.608 )
 
Bioon: Dear Professor Gomelsky, welcome to our conference. We know that optogenetics is a powerful tool to control neuronal activity in the brain. Near-infrared light can regulate the behavior of brain cells in a non-invasive way, but near-infrared light can only reach the shallow regions of brain, so how do you improve this technology to control the cells of deep tissue?
 
Professor Mark Gomelsky:  I am happy to take part in this Conference on Cell Therapy and to share my perspective on the applicability of optogenetics to cell therapy. Human tissues are poorly penetrable by visible light, yet light in the spectral region from 670 to 880 nm penetrates tissues better, much better than light of other wavelengths. This spectral region is known as Near-infrared Window (NIRW) or Therapeutic Optical Window. Light from external NIRW LEDs or lasers can reach brain regions through intact skull. Therefore, if NIRW light-responsive genes or engineered cells are delivered in the brain, they can be used for therapeutic purposes. How deep can NIRW penetrate through live brain tissue is not yet clear because such experiments have not been run. However, neurological illnesses represent only one of many potential applications of NIRW light optogenetics in cell therapy. No less exciting and potentially easier to implement are therapies that do not involve the brain. For example, human cells have been engineered to secrete peptide hormones in response to NIRW light irradiation. Such cells can be implanted under the skin in semi-permeable pouches that allow secreted hormones to reach the bloodstream but do not allow cell exchange between the pouch and the body. By regulating the duration of irradiation, a patient or a doctor will be able to control the dose of a hormone. Many illnesses involve hormonal imbalance, including diabetes, obesity, neurological and psychological illnesses. One can think about this type of therapy as a novel drug delivery platform, where a micro-pharmaceutical cell factory, which is located under a patient’s skin, produces therapeutic product on demand.
 

 
Bioon: Compared to the magnetic field and electric field used to stimulate brain cells, does the near-infrared light have some significant advantages?
 
Professor Mark Gomelsky:  In regard to neuronal stimulation, electro-magnetic therapies are fairly advanced, however not very specific. NIRW light optogenetics is not a therapy in itself, but a significant enhancement to gene and cell therapies. A gene or cell therapy enhanced by NIRW light optogenetics can supersede electro-magnetic stimulation in many ways. For example, a gene encoding a therapeutic function can be delivered into the specific brain region using viral-like particles and production of a therapeutic agent can be activated by NIRW light on demand. Several studies have now shown remarkable safety of AAV-based gene delivery into the brain, and injections of certain cells directly in the brain have proven safe as well. Therefore, the path of introducing NIRW light-controlled systems for the treatment of neurological disorders is open.
 
Bioon: What kind of diseases is the near-infrared light-activated optogenetics suitable for treating? Did the latest clinical trial based on the technology achieve some significant results?
 
Professor Mark Gomelsky: NIRW light-based optogenetics is a way to control the behavior of engineered cells with temporal and spatial precision that is hard to achieve via pharmacological (chemical) means. I have mentioned on-demand secretion of peptide hormones that can be used for treating diabetes, obesity and other illnesses. Treatment of immunological disorders and cancer could also benefit from NIRW optogenetics. For example, NIRW light-dependent anti-inflammatory Treg cells could help establish local zones of immune suppression in transplanted organs, which may help preserving such organs from rejection by the host. In immunooncology, it is possible to engineer light-controlled cancer-specific killer T cells (CAR-T or TCR) thus increasing safety of such therapies. At present, most of these venues are hypothetical; however, some are being pursued by our group and others using small animal models. I hope these pre-clinical studies will soon lead to the acceptance of NIRW light optogenetics in various clinical applications involving engineered cells. 
 
 
Bioon: As you said, near-infrared optogenetics method can be adapted for increasing safety of CAR-T and TCR immunooncology therapies. Could you explain how it could work?
 
Professor Mark Gomelsky:  One of the principal problems with CAR-T and TCR therapies, as well as with other therapies involving engineered cells, is the lack of effective ways to control activity of such cells after they have been injected or implanted in a patient’s body. Over-reactive CAR-T or TCR cells may kill tumors too aggressively resulting, for example, in a cytokine storm, or they can indiscriminately damage healthy organs. If killing activity of such cells can be suppressed by NIRW light, these cells will be a lot safer to use. Alternatively, killing activity can be turned on by light only at the desired body locations and for desired periods of time. Of course, for NIRW light optogenetics to work, tumors have to be accessible to light -- either external light or light guides inserted in the body to irradiate internal organs. Fortunately, NIRW light penetrates well through skin, bones and up to several centimeters of other human tissues. Furthermore, NIRW light has essentially no negative side effects at the doses needed to activate NIRW photoreceptors.
 

 
Bioon: What do you expect of to take home after attending this conference?
 
Professor Mark Gomelsky:   I am excited to present to the conference attendees the opportunities of NIRW light optogenetics and to share some of the tools developed in my laboratory. I hope that my talk will spark new ideas among meetings participants. In return, I expect to benefit from the insights of the attendees who have clinical experience with cell therapies. I would like to establish new collaborations that may ultimately accelerate the progression toward the clinic of the cell therapies enhanced by optogenetics. 


版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->