AAV4-Syn-GFP

Direct injection of AAV into the central nervous system (CNS) has been used to achieve high levels of transgene expression in different animal models. This AAV vector delivery strategy can be broadly divided into intracerebrospinal fluid (CSF) and intraparenchymal administration. The CSF performs multiple functions, providing nutrients; providing molecular and physical cues for important processes such as stem cell migration; and removing interstitial solutes from the brain parenchyma. Understandably, the use of AAV injection into the ventricles, cisterna magna, or intraspinal lumbar puncture allows for efficient delivery of reporter genes/therapeutic transgenes to large areas of the CNS.

Some AAV vectors exhibit highly cell-specific transduction characteristics when injected intracerebrospinal fluid. For example, intracerebroventricular (ICV) injection of AAV4 selectively targets astrocytes within the periventricular k-zone. The ependyma is composed of adult neural stem cells that have the ability to migrate, differentiate, and repopulate functionally defined areas of the brain throughout life. Indeed, targeted delivery of neurogenic cargo, e.g., noggin and brain derived neurotrophic factor (BDNF) packaged in AAV4 has shown long-term rescue of mouse models of severely debilitating CNS disorders like Huntington’s disease. In addition to these in vivo studies, biophysical analysis of the AAV4 capsid has revealed unique structural features and low capsid homology between other natural AAV isolates.