SCIENCE NEWS # 4

Name: Venice Claire O. Cabili Date: November 29, 2019

Grade & Section: 8 – Adelfa Group # 2

THE FITNESS LANDSCAPE OF AAV

Steve Mao

Computer-generated image of the atomic structure of adeno-associated virus

Adeno-associated virus (AAV) is an important gene therapy vector. Using tools from synthetic
biology, Ogden et al. provide a comprehensive view of how sequence changes in capsid proteins
affect AAV properties. After saturation mutagenesis of the AAV2 capsid gene, the resulting
library was subjected to multiplexed phenotypic analyses, including virus production, immunity,
thermostability, and biodistribution. The mutant distribution to major organs in mice revealed
dominant trends affecting in vivo delivery. Moreover, the findings uncovered a viral accessory
protein with a role in viral production. Finally, a model built from the capsid fitness landscape
enabled machine-guided design of useful variants with much higher efficiency than random
mutagenesis.

SOURCE:
Science, this issue p. 1139
https://science.sciencemag.org/content/366/6469/twis