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\begin{document}

\title{Rational design and experimental evaluation of peptide ligands for the
purification of adeno-associated viruses via affinity chromatography}



\author[1]{Shriarjun Shastry}%
\author[1]{WENNING CHU}%
\author[1]{Eduardo Barbieri}%
\author[1]{Paul Greback-Clarke}%
\author[1]{William Smith}%
\author[1]{Christopher Cummings}%
\author[1]{Ariann Minzoni}%
\author[1]{Jenifer Pancorbo}%
\author[1]{Gary Gilleskie}%
\author[2]{Kimberly Ritola}%
\author[1]{Michael Daniele}%
\author[1]{Stefano Menegatti}%
\affil[1]{NC State University}%
\affil[2]{UNC}%


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  \date{June 18, 2024}


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\begin{abstract}
Adeno-associated viruses (AAVs) have acquired a central role in modern
medicine as delivery agents for gene therapies targeting rare diseases.
While new AAVs with improved tissue targeting, potency, and safety are
being introduced, their biomanufacturing technology is lagging. The AAV
purification pipeline, in particular, hinges on protein ligands for the
affinity-based capture step: while featuring excellent AAV binding
capacity and selectivity, these ligands require strong acid (pH
\textless{}3) elution conditions, which can compromise the product's
activity and stability; additionally, their high cost and limited
lifetime has a significant impact on the price tag of AAV-based
therapies. Seeking to introduce a more robust and affordable -- yet
equally effective -- affinity technology, this study introduces a cohort
of peptide ligands that (i) mimic the biorecognition activity of the AAV
receptor (AAVR) and anti-AAV antibody A20, while (ii) enabling product
elution under near-physiological conditions (pH 6.0) and (iii) granting
extended reusability by withstanding multiple regenerations. A20-mimetic
CYIHFSGYTNYNPSLKSC and AAVR-mimetic CVIDGSQSTDDDKIC demonstrated
excellent capture of serotypes belonging to distinct clones/clades --
AAV1, AAV2, AAV5, AAV6, AAV8, and AAV9 -- corroborating the in silico
models documenting their ability to target regions of the viral capsid
that are conserved across all serotypes. CVIDGSQSTDDDKIC-Toyopearl resin
features binding capacity (\textasciitilde{}1014 vp per mL) and product
yields (\textasciitilde{}60-80\%) on par with commercial adsorbents, and
purified AAV2 from HEK293 and Sf9 cell lysates affording high recovery
(up to 78\%) and reduction of host cell proteins (up to 700-fold), and
high transduction activity (up to 65\%) of the purified vectors.%
\end{abstract}%



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\verb`Manuscript.docx`  available at \url{https://authorea.com/users/588939/articles/644968-rational-design-and-experimental-evaluation-of-peptide-ligands-for-the-purification-of-adeno-associated-viruses-via-affinity-chromatography}

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