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IGEM: Intelligently Genetically Engineered Microglia

Our ambitious project concerns bringing synthetic biology to the brain in order to try a novel approach to tackling Alzheimer’s Disease (AD). Microglia are mobile brain cells, making them an ideal chassis. To do this, our proposed treatment would involve extracting microglia from a patient, or using a specially bred immortalised line of human microglia, to avoid rejection, and transfecting it with our new genetic circuit. Implantation into the brain could be performed surgically or using a viral vector - but in order to better control the numbers of genetically engineered microglia (GEM) in the brain micro-neurosurgery may prove best. Our circuit is designed to detect detect amyloid plaques, attract other microglia, degrade the plaques, reduce neuroinflammation and support dying neurons. Theoretically, this should halt the progression of Alzheimer’s disease and could lead to other forms of neuro-genetic engineering.

Our GEM have zeocin resistance would be injected into the key areas of pathology in the AD brain; the neocortex, limbic structures, hippocampus, amygdala, and some of the brainstem nuclei. Microglia are naturally drawn towards the senile plaques characteristic of AD. Senile plaques create free radicals, so as the GEM near the plaques oxidative stress increases. In response, our oxidative stress promoter will increase the transcription of key genes. Their protein products are matrix metalloproteinase 9 (MMP-9) , vasoactive intestinal peptide(VIP), brain derived neurotrophic factor (BDNF) and a chemoattractant called interferon gamma-induced protein 10(IP-10).