Team:MIT/Delivery

From 2014.igem.org

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In the early stages of our research, we contacted several professionals in the field of neuro-biology and Alzheimer’s disease. Through several remote and face-to-face conversations [link to outreach - interviews)], we discussed and developed several potential delivery methods for the system we hoped to created. For the purpose of our system, there were two types of cells in the brain that we could consider as targets for modification: neurons and microglia.
In the early stages of our research, we contacted several professionals in the field of neuro-biology and Alzheimer’s disease. Through several remote and face-to-face conversations [link to outreach - interviews)], we discussed and developed several potential delivery methods for the system we hoped to created. For the purpose of our system, there were two types of cells in the brain that we could consider as targets for modification: neurons and microglia.
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<h2>Delivery to Neurons</h2>
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Delivery to Neurons
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Neurons are the main cells affected by Alzheimer’s disease. Direct modification of neurons would be beneficial, since beta-amyloid production occurs within these cells. Delivery of our system to neurons would require in vivo engineering of the cells (since neurons do not regenerate).  
Neurons are the main cells affected by Alzheimer’s disease. Direct modification of neurons would be beneficial, since beta-amyloid production occurs within these cells. Delivery of our system to neurons would require in vivo engineering of the cells (since neurons do not regenerate).  
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Delivery of our system to neurons would be most effective (and targeted) if administered via brain surgery. However, both spinal and blood injection are (less effective) options of viral/lipid delivery to neurons.
Delivery of our system to neurons would be most effective (and targeted) if administered via brain surgery. However, both spinal and blood injection are (less effective) options of viral/lipid delivery to neurons.
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<h2>Delivery to Microglia</h2>
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Delivery to Microglia
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Microglia are the immune cells of the brain. Direct modification of microglial precursor cells would be beneficial, since microglia are known to consume and degrade beta-amyloid. Delivery of our system to microglial precursor cells would allow for ex vivo engineering of the cells (which is safer, more effective and targeted than in vivo engineering).  
Microglia are the immune cells of the brain. Direct modification of microglial precursor cells would be beneficial, since microglia are known to consume and degrade beta-amyloid. Delivery of our system to microglial precursor cells would allow for ex vivo engineering of the cells (which is safer, more effective and targeted than in vivo engineering).  
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Delivery of our system to microglia would not require a quite as invasive method as brain surgery. Blood or spinal injection would be sufficient.
Delivery of our system to microglia would not require a quite as invasive method as brain surgery. Blood or spinal injection would be sufficient.
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<h2>Considering the public opinion</h2>
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Considering the public opinion
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While contemplating our potential delivery mechanisms, we also took into consideration that some methods might be more publicly acceptable than others. In the end, as a therapeutic, our system would be effective only if patients were willing to receive it.  
While contemplating our potential delivery mechanisms, we also took into consideration that some methods might be more publicly acceptable than others. In the end, as a therapeutic, our system would be effective only if patients were willing to receive it.  
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Hence, we constructed and distributed a survey to help us glean the public opinion of the three possible delivery mechanisms: brain surgery, spinal injection and blood injection. More details about our survey may be found here: [link to survey page]
Hence, we constructed and distributed a survey to help us glean the public opinion of the three possible delivery mechanisms: brain surgery, spinal injection and blood injection. More details about our survey may be found here: [link to survey page]
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<h2>Conclusion</h2>
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Conclusion
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Considering our research, the opinions of professionals and the results of our public opinion survey, we decided to pursue a system intended for delivery into neurons. Although this option requires the more risky in vivo engineering, it would allow for more targeted and effective delivery of our system, and (theoretically) a more potent effect on the symptoms of Alzheimer’s disease.  
Considering our research, the opinions of professionals and the results of our public opinion survey, we decided to pursue a system intended for delivery into neurons. Although this option requires the more risky in vivo engineering, it would allow for more targeted and effective delivery of our system, and (theoretically) a more potent effect on the symptoms of Alzheimer’s disease.  

Revision as of 20:15, 17 October 2014

 


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Delivery


Our system to detect and treat Alzheimer’s disease would potentially be a therapeutic for human patients. As such, we know that there needs to be a designated method of delivering the system into the human body. This is no trivial consideration: the necessary delivery method could have implications at many stages in the research and development process.

In the early stages of our research, we contacted several professionals in the field of neuro-biology and Alzheimer’s disease. Through several remote and face-to-face conversations [link to outreach - interviews)], we discussed and developed several potential delivery methods for the system we hoped to created. For the purpose of our system, there were two types of cells in the brain that we could consider as targets for modification: neurons and microglia.

Delivery to Neurons



Neurons are the main cells affected by Alzheimer’s disease. Direct modification of neurons would be beneficial, since beta-amyloid production occurs within these cells. Delivery of our system to neurons would require in vivo engineering of the cells (since neurons do not regenerate).

Possible vehicles for delivery to neurons include viral and lipid delivery. These methods are further described in these research papers [link to research papers].

Delivery of our system to neurons would be most effective (and targeted) if administered via brain surgery. However, both spinal and blood injection are (less effective) options of viral/lipid delivery to neurons.

Delivery to Microglia



Microglia are the immune cells of the brain. Direct modification of microglial precursor cells would be beneficial, since microglia are known to consume and degrade beta-amyloid. Delivery of our system to microglial precursor cells would allow for ex vivo engineering of the cells (which is safer, more effective and targeted than in vivo engineering).

Ex vivo engineering would occur completely in a laboratory setting and is possible because microglia regenerate. This type of modification would not require any specific delivery vehicle (since the vehicle will not be interacting with the human body).

Delivery of our system to microglia would not require a quite as invasive method as brain surgery. Blood or spinal injection would be sufficient.

Considering the public opinion



While contemplating our potential delivery mechanisms, we also took into consideration that some methods might be more publicly acceptable than others. In the end, as a therapeutic, our system would be effective only if patients were willing to receive it.

Hence, we constructed and distributed a survey to help us glean the public opinion of the three possible delivery mechanisms: brain surgery, spinal injection and blood injection. More details about our survey may be found here: [link to survey page]

Conclusion



Considering our research, the opinions of professionals and the results of our public opinion survey, we decided to pursue a system intended for delivery into neurons. Although this option requires the more risky in vivo engineering, it would allow for more targeted and effective delivery of our system, and (theoretically) a more potent effect on the symptoms of Alzheimer’s disease.

Our system is based mostly on the interactions of proteins and miRNA molecules. The proteins used may function in either neurons or microglia. In order to switch our system functionality from a neuron environment to a microglial environment, it would require modifying the miRNA sensed for [link to miRNA Detection] and used [link to treatment] in our various modules. However, it must be noted that, although our system is meant to target neurons, in the event that this method becomes undesirable, it is quite possible to (in theory, simply) modify the system to target microglial precursor cells via ex vivo engineering.

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