Samt leveranse teknologien som kan løse et/flere hindre i form av toxicity og til hvilke celler som er målet, (CNS) i det overnevnte tilfellet.
https://www.nature.com/articles/d43747-022-00180-9
Underpinning Voyager’s mission is its trademark AAV capsid-discovery platform, Tropism Redirection of AAV by Cell-type-specific Expression of RNA (TRACER). This broadly applicable, functional, RNA-based technology allows for rapid in vivo evolution of AAV capsids with desired cell-specific transduction properties in multiple species, including non-human primates (NHPs). TRACER facilitates the discovery of capsids that can cross the blood–brain barrier (BBB), have enhanced CNS tropisms across species, and achieve widespread biodistribution and transduction of multiple regions of the brain, including those that have traditionally been difficult to reach.
For example, using TRACER, Voyager has discovered a series of novel AAV capsids that, following intravenous (IV) administration, achieve up to 1,000-fold higher RNA expression in the brain and 100-fold higher RNA expression in the spinal cord of NHPs relative to AAV9, which is the naturally occurring AAV serotype that is currently understood to have the best penetration of the BBB in humans. “We believe Voyager’s TRACER capsids should allow significantly enhanced gene delivery to specific types of cells in the brain at lower doses than conventional AAV9".
In addition to their improved tropism for the target tissues, a number of the capsids discovered by Voyager demonstrate significantly reduced delivery to off-target tissues, such as the dorsal root ganglia or the liver, which may help avoid toxicities commonly associated with AAV delivery.
Preklinisk, I know, men med disse teknologiene kombinert kan man ytt ligere redusere dosene.
Ikke for å klippe og lime for mye, men Voyagers sin plattform har også funnet AAV kapsider som viser gen leveranse til både hjerte og øyet >
Using TRACER, Voyager is also identifying capsids with the capacity for strong cardiac and skeletal muscle transduction, and the platform holds promise for producing candidates with enhanced tropism for liver, eye, and other tissue types (Fig. 2). The company is proceeding with additional capsid campaigns derived from AAV9, AAV5, and other AAV serotypes to identify novel capsids optimized for AAV delivery for specific therapeutic applications.
