User talk:Hannah Kempton

Overview: siRNA Delivery Across the Blood Brain Barrier to treat Huntington's Disease

• Overview Sentence

Background

Blood Brain Barrier

• The blood brain barrier (BBB) plays a crucial role in modulating cerebral homeostasis and directing neuronal functions. It separates circulating blood from cerebrospinal brain fluid and prevents harmful toxins from reaching the brain.
• In other parts of the body, the thin endothelial cells lining vessel and capillary walls overlap at leaky junctions that are flexible enough to allow larger molecules like hormones, viruses, and bacteria to squeeze through the junctions or diffuse directly through the cells into the surrounding tissue.
• However, the endothelial cells lining blood vessels in the brain overlap at tight junctions and are surrounded by a thick basal membrane containing contractile pericytes as well as astrocytic glial cells that provide nutrients and play a role in brain and spinal cord repair. These cells are collectively known as the BBB.
• The BBB only allows small, essential hydrophobic molecules like O2 and glucose and essential ions like Na+, K+, and Cl- to pass from the blood to the brain and central nervous system (CNS), but prevents the passage of molecules greater than about 500 Da.

Nanodelivery

• Recently, the use of nanoparticles (NPs) has become increasingly common in solving environmental and medical problems, particularly in targeted drug delivery systems, among others
• Due to their size, NPs are unique in that their chemical, physical, and biological properties differ from that of their bulk materials, so they can be considered “new” material
• Significance of Nanoscience in Medicine
  • Higher surface area:volume ratio → nanomaterials have higher reactivity, mechanical strength, and magnetic or electrical properties
  • NPs able to cross BBB and mediate repair of BBB damage that may be responsible for diseases like Alzheimer’s
  • For our purposes, NPs may serve as an effective vector, containing siRNA or other drugs, for targeted drug delivery across the BBB

Significance

Central Idea: Bridging the Gap

• talk about our idea and its scientific context: combining developing field of nanotechnology to deliver siRNAs
• Typically, viruses are used: talk about why bad
• Will have many applications once the nanodelivery is optimized: for this study we will focus on delivering siRNAs for the purpose of therapeutics in Huntington's Disease, but the optimized siRNA delivery technique will be widely applicable

Huntington's Disease

• stuff about disease: why we selected Huntington's (social context: any improvement on current treatment is good)

Experimental Overview

siRNA

• explain we're not designing them just taking them from another paper that successfully used viral delivery

in vitro BBB mode

• explain justification for doing in vitro
• briefly describe selected model