Whole Brain AAV

Germline transgenics are powerful tools for performing causal manipulations of gene function; while CRISPR-based methods have made them newly accessible for many species, there are some applications for which they are not well suited. One interesting alternative is the recent advent of methods for the use of gene therapy vectors that are injected intravenously. AAV9 is known to have some natural ability to penetrate the blood-brain barrier, and researchers have generated AAV9 capsid variants that efficiently cross the blood-brain barrier and enter neurons in lab mice, enabling efficient whole-brain transduction. We plan to generate an evolved serotype capable of whole brain infectivity in voles. The value of this approach is that it allows remarkably simple brain-wide transformation, by-passing the need for stereotaxic surgeries or the development of new transgenic lines. Moreover, because these are not germline manipulations,