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Favorable safety profile of LV‐mediated intracerebral gene therapy

Published byTuomas Tikkanen Modified over 5 years ago

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Presentation on theme: "Favorable safety profile of LV‐mediated intracerebral gene therapy"— Presentation transcript:

1 Favorable safety profile of LV‐mediated intracerebral gene therapy
Favorable safety profile of LV‐mediated intracerebral gene therapy A, BLocal infiltration of CD3+ T cells, CD20+ B cells, and CD11c+ macrophages at the injection site of S1.2 NHP (A) and S2.3 NHP (B). Staining performed on the matched block of the contralateral hemisphere of S2.3 NHP has normal appearance and no detectable signs of inflammation (B). Scale bar, 100 μm.CCCL2 mRNA expression levels in the injected and contralateral hemispheres of LV.hARSA‐injected NHP of study group 1 (S1.2 and S1.3) and study group 2 (2.2 and 2.3). Values are expressed as fold to physiological (dotted line = 1), assessed in matched samples from untreated (UT) WT NHP. Data are expressed as mean ± SEM; n = 2 blocks/hemisphere/animal.DNeuron with large cellular body, homogenous eosinophilic cytoplasm (interpreted as intracytoplasmic accumulations) and lateral displacement of nucleus (arrows). Scale bar, 40 μm.EAntibodies against total LV particles in the pre‐ and post‐surgery sera (1:200 dilution) of LV‐injected NHPs. Values plotted in the graph are the mean of n = 5 technical replicates. Threshold (dotted line; 5.12 μg/ml) is set as the average titer measured in pre‐surgery sera plus three standard deviations.FAnti‐p24 and anti‐VSV‐G antibodies in the pre‐ and post‐surgery sera (1:20 dilution) of S2.1 and S2.3 NHP. Values plotted in the graph are the mean of n = 3 technical replicates. Threshold: 0 μg/ml.GAnti‐GFP antibodies in the pre‐ and post‐surgery sera (1:200 dilution) of pilot group NHP. Threshold: 0 μg/ml. Antibody titers are expressed in μg/ml. Sera of adult BALB/c mice immunized by systemic injection of LV.ET.GFP.miR‐142 (Annoni et al, 2009) were used as positive controls. Sera of untreated mice were used as negative controls.H, IPolyclonal LV integration profile in CNS tissues of LV‐injected NHPs. Clonal abundance is calculated as the sequencing reads representing each integration site within each data set. Gray bars represent all vector integrations with an abundance of < 1% (H). Relative proportions of LV integrations mapping inside and outside genes are indicated (I). Vasco Meneghini et al. EMBO Mol Med. 2016;8: © as stated in the article, figure or figure legend

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