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\begin{document}

\title{Infusion reactions to adeno-associated virus (AAV)-based gene therapy:
Mechanisms, diagnostics, treatment and review of the literature}



\author[1]{Kin Israel Notarte}%
\author[2]{Jesus Alfonso Catahay}%
\author[3]{Raymart Macaset}%
\author[1]{Jin Liu}%
\author[4]{Jacqueline Veronica Velasco}%
\author[4]{Princess Juneire Peligro}%
\author[4]{Jolaine Vallo}%
\author[5]{Nathaniel Goldrich}%
\author[2]{Lokesh Lahoti}%
\author[6]{Jiayan Zhou}%
\author[7]{Brandon Henry}%
\affil[1]{Johns Hopkins University Department of Pathology}%
\affil[2]{Saint Peter’s University Hospital}%
\affil[3]{Monmouth Medical Center}%
\affil[4]{University of Santo Tomas Faculty of Medicine and Surgery}%
\affil[5]{New York Medical College}%
\affil[6]{Stanford University Department of Medicine}%
\affil[7]{Cincinnati Children’s Hospital Medical Center}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\begin{abstract}
The use of adeno-associated virus (AAV) vectors in gene therapy has
demonstrated great potential in treating genetic disorders. However,
infusion-associated reactions (IARs) pose a significant challenge to the
safety and efficacy of AAV-based gene therapy. This review provides a
comprehensive summary of the current understanding of IARs to AAV
therapy, including their underlying mechanisms, clinical presentation,
and treatment options. Toll-like receptor activation and subsequent
production of pro-inflammatory cytokines are associated with IARs,
stimulating neutralizing antibodies and T-cell responses that interfere
with gene therapy. Risk factors for IARs include high titers of
pre-existing neutralizing antibodies, previous exposure to AAV, and
specific comorbidities. Clinical presentation ranges from mild flu-like
symptoms to severe anaphylaxis and can occur during or after AAV
administration. There are no established guidelines for pre- and
post-administration tests for AAV therapies, and routine laboratory
requests are not standardized. Treatment options include
corticosteroids, plasmapheresis, and supportive medications such as
antihistamines and acetaminophen, but there is no consensus on the route
of administration, dosage, and duration. This review highlights the
inadequacy of current treatment regimens for IARs and the need for
further research to improve the safety and efficacy of AAV-based gene
therapy.%
\end{abstract}%



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\textbf{Hosted file}

\verb`Notarte2023-AAV-Gene-Therapy-_KIN3.docx`  available at \url{https://authorea.com/users/638461/articles/654258-infusion-reactions-to-adeno-associated-virus-aav-based-gene-therapy-mechanisms-diagnostics-treatment-and-review-of-the-literature}

\textbf{Hosted file}

\verb`Figure. Notarte2023-AAV-Gene-Therapy-_KIN3.docx`  available at \url{https://authorea.com/users/638461/articles/654258-infusion-reactions-to-adeno-associated-virus-aav-based-gene-therapy-mechanisms-diagnostics-treatment-and-review-of-the-literature}

\textbf{Hosted file}

\verb`Table. Notarte2023-AAV-Gene-Therapy-_KIN3.docx`  available at \url{https://authorea.com/users/638461/articles/654258-infusion-reactions-to-adeno-associated-virus-aav-based-gene-therapy-mechanisms-diagnostics-treatment-and-review-of-the-literature}

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\end{document}

