Syn-NES-jRCaMP1b AAV (Serotype 9)

Adeno-associated virus (AAV) vectors have great potential for gene therapy applications due to their ability to transduce many different types of tissues and provide stable, long-term gene expression. Multiple serotypes of AAV have been identified, and more than 120 additional variants have been isolated from human and non-human primate tissues. Each of these variants has unique properties, providing a large number of potential vectors for gene therapy. Different AAV serotypes exhibit different tissue tropisms and transduction efficiencies. For example, AAV1 exhibits efficient muscle transduction, AAV6 shows promise for targeting the lung conducting airway epithelium, and AAV8 has impressive liver transduction.

The AAV serotype with the most interesting properties as a vector is the AAV based on the human-derived virus AAV9. Following intravenous injection, AAV9 exhibits broad systemic transduction, including efficient targeting of the heart, liver, and skeletal muscle. In addition, AAV9 is able to cross the blood-brain barrier and transduce cells such as neurons in the brain and spinal cord. Recently, AAV9 has been shown to use galactose as a cellular receptor through a series of in vitro binding and transduction assays. This observation was also confirmed by in vivo studies in the mouse airways, in which the abundance of free galactose residues was increased by enzymatic removal of galactose-bound sialic acid residues from the surface of airway cells. The increase in terminal galactose sugars available for conjugation resulted in robust transduction of conducting airway epithelial cells by AAV9, as well as enhanced transduction of the nasal epithelium.