Targeting siRNA to Microglia to Suppress PU.1 Expression and Reduce Neuroinflammation

Researchers here report on their development of a means to target microglia in the brain with small interfering RNA (siRNA) to reduce PU.1 protein expression. PU.1 is implicated in the regulation of inflammation in microglia, and a number of groups are attempting to produce a basis for therapies. Chronic inflammation driven by microglia is a feature of aging and neurodegenerative conditions. Unresolved, constant inflammation is disruptive of tissue structure and function, and the brain is no exception. Inflammation is thought to be an important factor in the onset and progression of the most common forms of neurodegeneration, including Alzheimer's disease. In a prior study researchers showed that blocking the consequences of PU.1 protein activity helps to reduce Alzheimer's disease-related neuroinflammation and pathology. The simplest way to test whether siRNA could therapeutically suppress PU.1 expression in microglia would have been to make use of an already available delivery device, but one of the first discoveries in the study is that none of eight commercially available reagents could safely and effectively transfect cultured human microglia-like cells in the lab. Instead the team had to optimize a lipid nanoparticle (LNP) to do the job. LNPs have four main components and by changing the structures of two of them, and by varying the ratio of lipids to RNA, the researchers were able to come up with seven formulations to try. Among the seven candidates, on...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs