A Guide to AAV Serotype Selection

Introduction

As a molecular biologist I repeatedly encountered a few questions when designing my AAV constructs. Which serotype should I select? Which promoter should I use? What is the WPRE, and is it necessary? This is the first in a series of reviews intended as an aid to the research community. At Vector Biolabs we’ve produced tens of thousands of custom AAVs and would like to apply that experience to your development challenges.

For a more general overview of AAV biology see our “Intro to AAV” page.

Over the past 20 years, AAV has been actively investigated as a preferred vector that can be modified to deliver transgenes (DNA/RNA) safely into a variety of cell- and tissue-types across many species including murine, rodent, canine, and non-human primates. There are approved AAV-based gene therapies to treat hemophilia type B, spinal muscular atrophy, retinal dystrophy, and macular-age degeneration. AAV infection of target tissue and cells depends on several factors: their serotype (differentiated by the antigenic properties of the different viral capsid proteins), transducibility (cell receptor and mode of cell entry) and the type of promoter driving expression of the transgene. This review will summarize the tissue tropism and transducibility of the different AAV serotypes. It is important to note that no one AAV serotype is exclusive to a particular tissue or cell-type. However, some AAV serotypes transduce certain tissues more effectively than other serotypes.

Below we have summarized a few notable features of each naturally occurring serotype and included a table summarizing their tissue tropism.