freeman
المـديـر العـــام
عدد المساهمات : 19244
تاريخ التسجيل : 05/01/2011
العمر : 64
الموقع : http://sixhats.jimdo.com/
 | موضوع: Programmable molecular nanorobots for treatment of Pain  الإثنين مارس 03, 2014 11:52 am | |
| Machines and computers have drastically altered our ability to do work and shape almost every aspect of reality. However, our ability to deploy machines that will interface directly with the biology of living organisms at the cellular and molecular levels is very limited. This interaction with biological processes within the organism is achieved at present using drugs. The drugs are usually selected by screens of random compounds and their structure cannot be intuitively linked with function. Therefore, adverse side effects could be hardly predicted.
Let us imagine we could design drugs capable of the following feats: count to 10 before engaging its target; communicate with other drugs; perform a census of drug molecules at the target site. Surely, this will dramatically increase the levels of therapeutic control and selectivity. Our colleagues recently reported the design and fabrication of logic-guided DNA-based nanorobots for controlled and programmable transport and release of cargo between biological points of origin and destination (Douglas et al., 2012). The robots are controlled by an aptamer-based gate, which requires one or more biological, chemical or physical cues as its cognate keys. Using these nanorobots, we demonstrated selective signal manipulation in both cancer and immune cells. In the present proposal our primary goal is to further expand this novel technology and design and fabricate nanorobots capable of carrying modulators of neuronal activity, and of releasing them in a programmable, logically controlled fashion. In particular, we will design aptamer keys that will target the nanorobots to release their cargo in response to specific modes of pathological neuronal activity, and, therefore, will modulate only the pathological activity, while sparing normal functions. Using DNA nanorobots, we will attempt to interfere with pathological hyperexcitable states in models of chronic pain and epilepsy.
In the nervous system, uncontrolled alteration of intrinsic and network excitabilities leads to severe interruption of normal neuronal function. The archetypical manifestations of such uncontrolled changes are expressed as chronic pain and epilepsy. These devastating medical conditions reaching pandemic scale, lead to extreme suffering, as well as to exorbitant medical expenses. Despite extensive efforts, effective treatment for chronic pain and epilepsy remains elusive. Most current analgesic and antiepileptic drugs help in relieving the symptoms by nonspecific blockade of neuronal activity , thus having unwanted effects on normal function. Moreover, the action of current drugs is not initiated by endogenous signals and is not temporally or spatially tuned to selectively block the abnormal states. It is therefore essential to design treatment strategies that selectively target the aberrant processes causing chronic pain or epileptic seizures. We propose to use novel, cutting-edge technologies to design programmable DNA nanorobots that can sense specific modes of neuronal activity and respond by releasing selected modulators, thus affecting only pathological events. Using nanorobots, we will attempt to interfere with pain and seizure generation at multiple levels.
Using nanorobot-based platform we will strive to affect abnormal neuronal activity at the peripheral terminal of sensory neuron, the peripheral axon, neuronal cell bodies at dorsal root ganglion. We will also attempt to modulate abnormal synaptic transmission within the spinal cord, hippocampus and cerebral cortex. Implementing Boolean digital logic design we will temporally tune nanorobots to intervene at the onset of abnormal neuronal activity. Moreover, based on activity of specific neuronal pathways or the neuro- and gliotransmitter signature of circuits, we will manipulate programmable nanorobots to selectively modify these pathways. We then can study the functional properties of these pathways using behavioural or cutting edge electro-optical techniques, currently used in our laboratories. In this platform, the endogenous activity of specific neuronal pathways will ignite the robots. This entails an autonomous mechanism that has an inherent feedback loop, and is activated without the need for an external energy source.
In summary, this multidisciplinary project incorporates ground-breaking nano-technologies together with electrophysiological, multiphoton imaging and behavioural methodologies, which have been fine-tuned to study and control pain- and epilepsy-related mechanisms. The results of this proposal are expected to provide a basis for novel platforms for treating chronic pain and epilepsy, as well as to yield fundamental insights into the mechanisms of hyperexcitable states.
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لا أحد يظن أن العظماء تعساء إلا العظماء أنفسهم. إدوارد ينج: شاعر إنجليزي
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