Optogenetics – Innovation in Biotechnology and Neuroscience

Optogenetics – Innovation in Biotechnology and Neuroscience

Cami Rosso 25/02/2018 4
How the light and genetics may treat brain disorders in the future? Imagine being able to treat neurodegenerative diseases and mental disorders such as Alzheimer’s disease, Parkinson’s, epilepsy, PTSD, depression, and anxiety with non-invasive light-based therapy. This is the quest of pioneering scientists and researchers in optogenetics, an emerging field in biotechnology that uses light to control cells in living tissues such as neurons, in order to study brain function.

British Nobel laureate Francis Crick of The Salk Institute for Biological Studies in La Jolla, California put forth the concept of the ability to turn the firing of “one or more types of neuron on and off in the alert animal in a rapid manner” by using light as “the ideal signal” in his paper “The impact of molecular biology on neuroscience” published in Philosophical Transactions of the Royal Society B in 1999. Crick noted that his concept might be somewhat “far-fetched.” Yet as improbable as it would seem to the brightest minds in science before the turn of the century, this idea was proven in a little over half a decade. 

In optogenetics, scientists add genetic code to target tissue, typically a neuron, which enables it to make light-responsive proteins called opsins. Gero Miesenböck and Boris Zemelman published a study in 2002 titled “Selective photostimulation of genetically charged neurons” in Neuron. They used opsin from the retina of a fruit fly to make a neuron light-sensitive. A year later, they demonstrated the use of heterologous proteins to sensitize neurons to light [1]. Peter Hegemann, Georg Nagel and other researchers published their discovery of phototaxis and photophobic responses of green algae in 2002 [2]. In August 2005, MIT neuroscientist Ed. Boyden, PhD, along with Karl Deisseroth, Feng Zhang, Georg Nagel, and Ernst Bamberg published in Nature Neuroscience a landmark breakthrough in optogenetics, “Millisecond-timescale, genetically targeted optical control of neural activity.” Neurons inserted with opsin from green algae Chlamydomonas reinhardtii, called channelrhodopsin-2 (ChR2), turned on when exposed to blue light, and turned off when the light was removed [3]. This discovery paved the way for other researchers in neuroscience and biomedicine. 

In 2016, Boyden, Li-Huei Tsai, and other researchers published “Gamma frequency entrainment attenuates amyloid load and modifies microglia” in Nature which describes how amyloid plaques diminished using optogenetic techniques. What was even more ground-breaking was that they also discovered they could achieve similar results using optical light exposure without optogenetics [4]. More research is underway in this area as a possible future treatment for Alzheimer’s disease.

In a September 2017 interview with Eric J. Topol, MD published on Medscape, Boyden stated that there are “a couple of companies that have already begun, or are about to begin, clinical trials in humans.” Boyden mentioned Texas-based biotech RetroSense Therapeutics, purchased by Allergan in 2016, as one example. According to STAT, RetroSense’s clinical trial was not only the first time optogenetics have been used in humans, but also it was the first time non-human DNA was put into a human [5]. In this case, algae DNA was put in a virus, then injected in the human retina cells with the goal to treat retinitis pigmentosa, a rare disease that causes blindness [6].

On February 9, 2018, a global team of researchers from Japan, Singapore, and the USA published in Science, “Near-infrared deep brain stimulation via upconversion nanoparticle – mediated optogenetics.” This study was a milestone in optogenetics because it demonstrated the use of injecting nanoparticles into the ventral tegmental area (VTA) of a rodent brain. Instead of using a blue laser to activate the ChR2 in dopaminergic neurons, they used a less invasive technique with infrared light delivered at a distance of several millimeters outside the skull that resulted in the ability to stimulate dopamine release in the VTA, triggered memory recall, and neuromodulated hippocampal excitatory cells.

Today optogenetics is being used for research in neuroscience, behavioral science, cardiology, ophthalmology and other areas. The global optogenetics market is estimated to grow at a CAGR of 17.7 percent and reach USD 46.82 million by 2022 according to Stratistics MRC. Optogenetics is an innovative technology that is enabling neuroscientists and biomedical researchers to study how the brain works in hopes of discovering novel, less-invasive treatments for neurological disorders. 

References

1. Zemelman, Boris V.; Nesnas, Nasri,; Lee, Georgia A.; Miesenböck, Gero. “Photochemical gating of heterologous ion channels: Remote control over genetically designated populations of neurons.” Neuroscience. 2003 Jan 22.

2. Nagel, Georg; Ollig, Doris; Fuhrmann, Markus; Kateriya, Suneel; Musti, Anna Maria; Bamberg, Ernst; Hegemann, Peter. “Channelrhodopsin-1: A Light-Gated Proton Channel in Green Algae.” Science. 2002-06-28.

3. Lim, Diana H. and LeDue, Jeffrey. “What is Optogenetics And How Can We Use It To Discover More About The Brain?” Frontiers Young Minds. Volume 5, Article 51. September 2017. 

4. Preston, Elizabeth. “A Neurobiologist Thinks Big – and Small.” Quanta Magazine.January 18, 2018.

5. Swetlitz, Ike. “Optogenetics startup RetroSense bought by Allergan for $60 million.” STAT. September 6, 2016. 

6. Ibid.

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  • Chris Sulivan

    Optogenetics is a burgeoning field in the life sciences that scientists are very excited about. Scientists are looking to use versions of this tool to control Parkinson's, restore sight, and even to one day remotely control our brain's responses to things like fear, pain, and anxiety.

  • Jane Hawley

    One of the biggest limitations of optogenetics is how invasive it is with the fibre optic cables that have to be inserted directly to the neurons scientists want to target. This can cause tissue damage, especially when they are trying to control neurons deep within the brain.

  • Stephanie Ephraim

    very informative

  • Kevin Armstrong

    This technology still has a lot of time left in the lab before it can help to address human diseases

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Cami Rosso

Science Guru

Cami is a founder of three companies in high-tech consulting, global venture capital, and strategic marketing. She founded her first company during college and had a state branch of the Department of Aviation as her customer. She was a Kauffman Fellows semi-finalist. She has worked in Silicon Valley, Wall Street and globally for great companies like Apple, Morgan Stanley, PepsiCo, Adobe, and Oracle, to name a few. Cami was an American business delegate to the APEC/PECC IT summit of world leaders. She was an invited guest to meet an ambassador and diplomats to a Mission of the United Nations. Cami's speaking experience includes TV, radio, academia and industry conferences. She earned an MBA from IMD in Switzerland and a certificate in Marketing Innovative Technologies at the Harvard Business School Executive Education Program. She was recognized by The Financial Times and Radio Switzerland for her contribution to an award-winning team humanitarian project for children in UNHCR refugee camps.

   

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