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Successful liver transduction by re-administration of different adeno-associated virus vector serotypes in mice. | LitMetric

AI Article Synopsis

  • Intravenous gene therapy using adeno-associated virus (AAV) vectors is promising for treating genetic diseases, but re-administering the same AAV type is complicated due to the body's immune response creating neutralizing antibodies (NAbs).
  • Researchers tested liver-targeting AAV serotypes (AAV3B, AAV5, and AAV8) in mice to see if switching serotypes allows for successful re-administration.
  • Results showed that while NAbs were generally specific to the initially administered AAV, switching to a different serotype allowed for effective re-administration, revealing a potential strategy for future gene therapies.

Article Abstract

Background: Intravenous administration of adeno-associated virus (AAV) vectors is a promising gene therapy approach for monogenic diseases. However, re-administration of the same AAV serotype is impossible because of the induction of anti-AAV neutralizing antibodies (NAbs). Here, we examined the feasibility of re-administrating AAV vector serotypes different from the initial AAV vector serotype.

Methods: Liver-targeting AAV3B, AAV5, and AAV8 vectors were intravenously injected in C57BL/6 mice, and the emergence of NAbs and the transduction efficacy following re-administration were evaluated.

Results: For all serotypes, re-administration of the same serotype was not possible. Although the highest neutralizing activity of NAb was induced by AAV5, anti-AAV5 NAbs did not react with other serotypes, resulting in successful re-administration with the other serotypes. AAV5 re-administration was also successful in all mice treated with AAV3B and AAV8. Effective secondary administration of AAV3B and AAV8 was observed in most mice initially administrated AAV8 and AAV3B, respectively. However, few mice developed NAbs cross-reacting with the other serotypes, especially those with close sequence homology.

Conclusions: In summary, AAV vector administration induced NAbs relatively specific to the administrated serotype. Secondary administration of AAVs targeting liver transduction could be successfully achieved by switching AAV serotypes in mice.

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Source
http://dx.doi.org/10.1002/jgm.3505DOI Listing

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