Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection.
By C. Zincarelli, S. Soltys, G. Rengo, J. Rabinowitz. Molecular Therapy, 2008
1,426 citations recorded by the source corpus.
This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1-9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.
Subfields: Cardiology and Cardiovascular Medicine, Epidemiology, Genetics
View Paper: https://www.semanticscholar.org/paper/b106d86ecde4c59e34f2505c4764a852474826e1
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Citations in the corpus
- Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018, background): “Especially, AAV can be flexibly constructed to target specific organs or tissues based on the diverse tissue tropism of AAV serotypes [66, 67].”
- In vivo genome editing using Staphylococcus aureus Cas9 (2015, background): “For this purpose, adeno-associated virus (AAV) vectors are attractive vehicles 10 because of their low immunogenic potential, reduced oncogenic risk from host-genome integration 11 , and broad-range of serotype specificity 12–15 .”
- Engineering the Delivery System for CRISPR-based Genome Editing (2018, background): “This allows researchers to chose the optimal serotype to improve targeted delivery to their organ of interest [30].”