Making Darwin proud

In the past, gene therapy has been limited in how vectors can target cells for inter-species protein expression. Recently, Tabebordbar and colleagues discovered a promising way using evolution to generate highly specific adeno-associated virus (AAV) vectors.

The strategy of directed evolution of AAV capsids leveraging in vivo expression of transgene RNA (DELIVER) couples capsid library generation with in vivo transcript-based selection. Here’s Tabebordbar and his team’s DELIVER method:

1 – Using an AAV option, add 7-mer random peptide between 588–599 of cap

2 – Inject the library into your model, then identify the highly expressed capsid variants in your tissue of interest

3 – Do a second round with new variants as well as variants encoded by a synonymous DNA codon from the first round

4 – DELIVER the library into your model, then identify the highly expressed capsid variants in your tissue of interest

5 – Identify top muscle-tropic variants

The DELIVER method has numerous advantages. It selects AAV viruses that functionally transduce various tissues, it can be applied in many mammalian species, it has numerous preclinical animal applications, and can be used to develop diverse screening libraries. For example, Tabebordbar and his team used this approach to generate AAV9 and AAVrh74, which more effectively transduce muscle cells than the AAV variant initially used.

Our team at VectorBuilder recently shared how members of our community can use AAV Capsid Evolution in their research. Check out what we have learned, and email service@vectorbuilder.com to share how you are using this innovative approach in your lab.