The goal of Nastech's tight junction biology program is to understand the structure and function of these tissue barriers and to identify active compounds or excipients that can reversibly open tight junctions, thus permitting drugs to pass through. The goals of Nastech's research and development programs are to: 

• Increase the size of drug molecules that can be delivered (for example, proteins and oligonucleotide drugs)
• Improve the amounts delivered to the bloodstream
• Facilitate direct delivery to the central nervous system (CNS)

Tight junctions are the connections between epithelial and endothelial cells that comprise various tissues of the body. They regulate the passage of molecules across these natural barriers. Large molecular weight drugs need to pass through these tissue barriers in order to get to their sites of action. As part of the body's normal activity, tight junctions selectively open and close in response to various signals both inside and outside of cells. This allows the passage of large molecules or even entire cells across the tight junction barrier.

Tight junctions consist of proteins, for example, claudins, occludins and junctional adhesion molecules that are anchored in the membranes of two adjacent cells and interact with each other to hold the cells together and prevent other molecules from passing between them. Tight junction membrane proteins interact with scaffold proteins (e.g., ZO-1) to connect them with various signal transduction and transcriptional pathways involved in the regulation of tight junction function.

Tight junctions are found in all tissues, but those of particular relevance to drug delivery include:

• Nasal tissue
• Gastrointestinal tissue - where oral drugs are absorbed
• Blood vessels
• Blood-brain barrier

Nastech is using three fundamental, state-of-the-art technologies to understand tight junction biology and develop drug delivery solutions:

• RNA interference or RNAi, to determine which tight junction proteins are most important as targets for drug delivery
• Gene cloning and expression, to produce pharmaceutical quantities of the most important tight junction proteins. These proteins are identified by RNAi experiments, as high throughput screening tools for excipient formulation development
• High-throughput tissue culture assays for identifying compounds that reversibly increase drug permeation through tissue barriers (see Formulations Science.)