# Quantitative Analysis and Predictive Modeling of Nonspecific Adsorption of Recombinant Adeno-Associated Virus onto Solid Surfaces

## TL;DR

This study identifies factors causing rAAV virus adsorption onto surfaces and develops a model to predict and reduce it, improving gene therapy manufacturing.

## Contribution

A predictive model and surface modification strategy to minimize rAAV nonspecific adsorption during manufacturing.

## Key findings

- Both electrostatic and hydrophobic interactions contribute to rAAV adsorption.
- A hydrophilic and near-neutral surface coating effectively suppresses rAAV adsorption.
- The model and strategy work across multiple rAAV serotypes and commercial formulation conditions.

## Abstract

Recombinant adeno-associated virus (rAAV) has been increasingly
employed for in vivo gene therapy. To ensure the
particle concentration meets specifications, strategies are necessary
to minimize nonspecific adsorption of rAAVs onto solid surfaces during
manufacturing and drug-product dispensing into vials. In this study,
we first elucidated the physicochemical factors contributing to nonspecific
adsorption of rAAVs by evaluating their adsorption on model surfaces
with systematically controlled hydrophilicity and surface charge.
Subsequently, we constructed a predictive model through multiple regression
analysis of rAAV adsorption under various formulation conditions and
the physicochemical parameters of both rAAV serotypes and investigated
surfaces. The results revealed that both electrostatic and hydrophobic
interactions were responsible for rAAV adsorption. Consequently, we
designed a hydrophilic and near-neutral surface coating, which greatly
suppressed the adsorption of multiple rAAV serotypes, even under the
formulation conditions of marketed products, demonstrating the high
versatility and predictive accuracy of the model. These findings validated
the effectiveness of the surface modification strategy developed to
ensure the stable manufacturing and quality control of rAAV products,
offering a foundation for further material development toward clinical
applications.