AAV vector distribution in the mouse respiratory tract following four different methods of administration

BMC Biotechnology
Lisa A SantrySarah K Wootton

Abstract

Targeted delivery of gene therapy vectors to the mouse respiratory tract is often performed via intranasal or intratracheal administration; however, there can be a great deal of variability between these methods, which could potentially influence experimental results. Improving the accuracy and precision of lung delivery will not only reduce the number of animals required to detect statistically significant differences, but may reduce the variability of studies from different laboratories. Here we evaluated three different methods of adeno-associated virus (AAV) vector administration to the respiratory tract in mice (intranasal, intubation, and intratracheal injection) and discuss the advantages, challenges, and shortcomings of each. We also present a modified-intranasal delivery technique that is superior to passive administration of vector into the nares of anesthetized supine animals. Transgene expression was consistently visible in the nasal cavity, trachea, and proximal to middle aspect of all lung lobes for all four methods, whereas transgene expression was consistently observed in the most distal aspect of lung lobes only with the intubation and intratracheal injection techniques. AAV vector genome copy numbers in the lu...Continue Reading

References

Feb 21, 2002·Journal of the National Cancer Institute·Michael J ThunCarlo Patrono
Mar 7, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·D S SouthamM D Inman
Jul 27, 2004·Nature Medicine·Paul GregorevicJeffrey S Chamberlain
Jan 6, 2012·The International Journal of Neuropsychopharmacology·Esther BerrocosoJuan Antonio Mico

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Citations

May 19, 2019·Disease Models & Mechanisms·Liesbeth VanherpGreetje Vande Velde
Aug 18, 2020·Human Gene Therapy·Ana CarneiroDavid V Schaffer
Mar 12, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ami PatelDavid B Weiner
Aug 9, 2020·Nature Communications·Martin H KangBernard Thébaud
Aug 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yong Joon KimJoon Kim
May 23, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Konstantin Kochergin-NikitskySvetlana Smirnikhina

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Methods Mentioned

BETA
PCR
Assay

Software Mentioned

Graphpad
Graphpad Prism

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