A convenient enzyme-linked immunosorbent assay for rapid screening of anti-adeno-associated virus neutralizing antibodies

Ito, Takahiro; Yamamoto, Shigekazu; Hayashi, Tsukasa; Kodera, Mika; Mizukami, Hiroaki; Ozawa, Keiya; Muramatsu, Shin‐ichi

doi:10.1258/acb.2009.009077

Cited by 19 publications

(18 citation statements)

References 5 publications

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“…The samples derived from experiments performed at Selecta Bioscience were analyzed with a different AAV8 antibody assay 60 and results are expressed as EC50 titers or top OD value. Briefly, 96-well plates were coated overnight with AAV8 vector at 2.2 × 10 9 vg ml −1 , washed and blocked with 1% casein the following day, then diluted serum samples (1:40) added to the plate and incubated overnight.…”

Section: Methodsmentioning

confidence: 99%

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

et al. 2018

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Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses. This allows successful vector re-administration in mice and nonhuman primates. SVP[Rapa] dosed with AAV vectors reduces B and T cell activation in an antigen-selective manner, inhibits CD8+ T cell infiltration in the liver, and efficiently blocks memory T cell responses. SVP[Rapa] immunomodulatory effects can be transferred from treated to naive mice by adoptive transfer of splenocytes, and is inhibited by depletion of CD25+ T cells, suggesting a role for regulatory T cells. Co-administration of SVP[Rapa] with AAV vector represents a powerful strategy to modulate vector immunogenicity and enable effective vector re-administration.

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Section: Methodsmentioning

confidence: 99%

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

et al. 2018

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“…Alleviation of motor symptoms associated with PD was observed in both trials. In the UCSF study, 7 a low dose cohort of five patients received 110 11 vector genome (vg) and a high dose cohort of five patients received 310 11 vg of AAV–AADC. The mean improvements of the ten patients in the total score of unified Parkinson's disease rating scale (UPDRS) were 31% (10.5 points) in the off–state and 32% (10 points) in the on–state.…”

Section: Gene Transfer Of Dopamine–synthesizing Enzymesmentioning

confidence: 99%

“…Positron emission tomography (PET) using [ 18 F]fluoro–m–tyrosine (FMT), a tracer for AADC, revealed a 30 and 75% increase in Kic values in the putamen of the low–dose and high–dose cohort, respectively, at 6 months after the gene delivery. In the JMU study, six patients received 310 11 vg of AAV–AADC. Motor function in the off–state improved to a mean of 46% (11.6 points) based on the UPDRS scores at six months after surgery, without any apparent changes in the short–duration response to levodopa.…”

Section: Gene Transfer Of Dopamine–synthesizing Enzymesmentioning

confidence: 99%

“…The first six patients entered into the study receiving a dose of 310 11 vg, while the next six patients received a dose of 5.410 11 vg of AAV vector. A mean improvement of 36% (14 points) in the UPDRS motor score in the off–state and a mean increase of 25% (2.3 h) in on time without troublesome dyskinesia were observed one year after surgery.…”

Section: Gene Transfer Of Dopamine–synthesizing Enzymesmentioning

confidence: 99%

“…9 No clear pathogenicity in humans has been reported, and many adults synthesize antibodies against AAVs following latent infection in childhood. 10,11 The AAV genome exists in episomes in the nucleus and is rarely incorporated in the chromosomes. To date, more than one hundred genotypes have been defined for primate AAVs.…”

Section: Introductionmentioning

confidence: 99%

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The current status of gene therapy for Parkinson's disease

Muramatsu

2010

ANS

Self Cite

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The recent development of viral vectors, especially vectors derived from adeno–associated virus (AAV), has translated gene therapy for Parkinson's disease (PD) from animal experiments into clinical trials. The current gene therapy protocols used are based on three major strategies. The first protocol involves local production of dopamine via the introduction of dopamine–synthesizing enzyme genes into the putamen. The aromatic L–amino acid decarboxylase (AADC) gene has been transferred in this manner with the aim of efficiently converting orally administered L–dopa. The delivery of triple genes including tyrosine hydroxylase (TH), guanosine triphosphate cyclohydrolase I (GCH) and AADC is also being undertaken, and is aimed at continuously supplying dopamine into the putamen. The second protocol involves the protection of nigrostriatal projections via the production of neurturin, a trophic factor for dopaminergic neurons in the putamen. The final method includes the modulation of neural activity along the output pathway of the basal ganglia by transducing the subthalamic nucleus with vectors expressing glutamic acid decarboxylase (GAD–65, GAD–67), a key enzyme required for the synthesis of the inhibitory transmitter –aminobutyric acid (GABA). The initial results of phase 1 studies using AAV vectors have not only confirmed the safety of these vectors, but have also revealed the alleviation of motor symptoms associated with PD.

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Cell-Based Measurement of Neutralizing Antibodies Against Adeno-Associated Virus (AAV)

Jungmann

Müller

Rapti

2016

Methods in Molecular Biology

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In recent years gene therapy using adeno-associated viral (AAV) vectors to treat cardiac disease has seen an unprecedented surge, owing to its safety, low immunogenicity relative to other vectors and high and long-term transduction efficiency. This field has also been hampered by the presence of preexisting neutralizing antibodies, not only in patients participating in clinical trials but also in preclinical large animal models. These conflicting circumstances have generated the need for a simple, efficient, and fast assay to screen subjects for the presence of neutralizing antibodies, or lack thereof, in order for them to be included in gene therapy trials.

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A convenient enzyme-linked immunosorbent assay for rapid screening of anti-adeno-associated virus neutralizing antibodies

Cited by 19 publications

References 5 publications

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration

The current status of gene therapy for Parkinson's disease

Cell-Based Measurement of Neutralizing Antibodies Against Adeno-Associated Virus (AAV)

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