Intravenous infusion of AAV for widespread gene delivery to the nervous system

Abstract

The central nervous system (CNS) is a fascinating and intricate set of biological structures that we have yet to fully understand. Studying the in vivo function of the CNS and finding novel methods for treating neurological disorders have been particularly challenging. One difficulty is correcting genetic disorders afflicting the CNS in a targeted manner. Recombinant adeno-associated viruses (rAAVs) have emerged as promising therapeutic tools for treating genetic defects of the CNS, due to their excellent safety profile and ability to cross the blood-brain barrier (BBB). While stereotactic injection of AAV is promising for localized gene delivery, it is less desirable for some applications because of the technique’s invasiveness and limited intraparenchymal spread. Alternatively, intravascular administration can achieve widespread delivery of rAAV to the CNS. In this chapter, we will discuss the prevalent routes of administration to deliver rAAV to the CNS via intravenous (IV) injection in mice. We will highlight key considerations for using rAAV, and the advantages and disadvantages of each administration method. We will also briefly discuss intravenous delivery in larger animal models, factors that may impact experimental interpretations, and outlooks for clinical translation.