mouse balb cj strain 000651  (Jackson Laboratory)

Journal: Molecular Therapy. Nucleic Acids

Article Title: AAV9-mediated targeting of natural antisense transcript as a novel treatment for Dravet syndrome

doi: 10.1016/j.omtn.2026.102942

Figure Lengend Snippet: In vitro assessment of new AntagoNAT sequences (A) Schematic of AAV-CMV-eGFP-miR-155-AntagoNAT-miR-155-WPRE plasmid. (B) Transient transfection revealed 13 sequences to significantly increase Scn1a expression compared to the control cells (∗ p < 0.001). Candidates K, H, and J showed the highest increase in expression (16-fold compared to control). One-way ANOVA with multiple comparison correction using Two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli. n = 9/10 for AntagoNAT sequences, n = 6 for control (3 technical replicates each). (C) Schematic of AAV-U6-AntagoNAT-CMV-eGFP-WPRE plasmid. (D) In vitro transduction of AAV9 vectors ( n = 5/6 replicates of each group, 3 technical replicates each) using either the U6 or the CMV promoter, represented in a Boxplot. One-way ANOVA, Dunnett’s multiple comparison performed.

Article Snippet: 129 S- Scn1a tm1Kea /Mmjax DS mouse strain, which contain an exon 1 deletion of Scn1a , resulting in haploinsufficiency, were obtained from the Jackson Laboratory (Jackson Laboratory, ME, USA).

Techniques: In Vitro, Plasmid Preparation, Transfection, Expressing, Control, Comparison, Transduction

Journal: Molecular Therapy. Nucleic Acids

Article Title: AAV9-mediated targeting of natural antisense transcript as a novel treatment for Dravet syndrome

doi: 10.1016/j.omtn.2026.102942

Figure Lengend Snippet: Neonatal AAV9-AntagoNAT-H gene therapy increases survival and reduces febrile seizures in DS mice Scn1a +/− mice received either AAV9-AntagoNAT-H or PBS via i.c.v. and i.v. PBS was also administered to wild-type mice ( Scn1a +/+ ). (A) Experiment timeline. (B) Survival of Scn1a +/− DS mice treated with AAV9-AntagoNAT-H ( p = 0.04), shown in percentage of survival. Log-rank (Mantel-Cox) test. (C) Weight curves, data presented as mean, with SD error bars. Two-way ANOVA with Dunnett’s multiple comparisons test. (D) Febrile seizure temperature threshold assessment, showing a significant reduction with AAV9-AntagoNAT-H treated group ( p < 0.001). Log-rank (Mantel-Cox) test. (E) Duration of febrile seizures reduced in AAV9-AntagoNAT-H group ( p < 0.001). Man-Whitney test. (F) The Racine score classification of febrile seizures observed in the experimental mice. A significant reduction in seizure severity was observed in AAV9-AntagoNAT-H group ( p = 0.02). Fisher's exact test.

Article Snippet: 129 S- Scn1a tm1Kea /Mmjax DS mouse strain, which contain an exon 1 deletion of Scn1a , resulting in haploinsufficiency, were obtained from the Jackson Laboratory (Jackson Laboratory, ME, USA).

Techniques:

Journal: Molecular Therapy. Nucleic Acids

Article Title: AAV9-mediated targeting of natural antisense transcript as a novel treatment for Dravet syndrome

doi: 10.1016/j.omtn.2026.102942

Figure Lengend Snippet: Increase of endogenous Scn1a in the cortex of AAV9-AntagoNAT-H-treated Scn1a +/− DS mice (A) Scn1a expression in the cortex, significantly increased with AAV9-AntagoNAT-H ( p = 0.032) and Scn1a +/+ PBS ( p = 0.003) compared to PBS group. (B) Scn1a expression in the heart showed a signifcant difference between Scn1a +/+ PBS and Scn1a +/− group ( p < 0.001) only. (C) Vector copy number analysis in the cortex showed a significant increase in AAV9-AntagoNAT-H group ( p < 0.001). (D) Vector copy number in the heart only revelaed a signifcant difference between Scn1a +/+ and Scn1a +/ − PBS groups ( p < 0.001). (E) Na V 1.1 expression in the cortex. One-way ANOVA Holm-Šídák’s multiple comparisons test. For each group, n values are indicated in the figure.

Article Snippet: 129 S- Scn1a tm1Kea /Mmjax DS mouse strain, which contain an exon 1 deletion of Scn1a , resulting in haploinsufficiency, were obtained from the Jackson Laboratory (Jackson Laboratory, ME, USA).

Techniques: Expressing, Plasmid Preparation

Journal: Molecular Therapy. Nucleic Acids

Article Title: AAV9-mediated targeting of natural antisense transcript as a novel treatment for Dravet syndrome

doi: 10.1016/j.omtn.2026.102942

Figure Lengend Snippet: Increase in endogenous Scn1a after i.c.v. and i.v. AAV9-AntagoNAT-H therapy to P14 Scn1a +/− DS mice (A) Schematic diagram showing the experimental plan. (B) Survival curve for AAV9-H dose D, showing percentage of survival. (C) Representative images of GFAP (top) and CD68 (middle) staining in the brain and CD68 in the liver (bottom) of animals that received AAV9-H dose D. Further details in . (D) Survival curve of animals that received AAV9-H dose E, showing percentage of survival. Log-rank (Mantel-Cox) test. (E) Scn1a expression in cerebral cortex displayed a significant increase in both Scn1a +/+ PBS and Scn1a +/ − AAV9-AntagoNAT-H groups ( p = 0.009) compared to Scn1a +/ − PBS group. Cerebral cortex tissues for Scn1a +/− group, range from P20 to 100. (F) Na V 1.1 expression in the cerebral cortex, reported a difference between control groups only ( p = 0.013). One-way ANOVA Holm-Šídák’s multiple comparisons test.

Article Snippet: 129 S- Scn1a tm1Kea /Mmjax DS mouse strain, which contain an exon 1 deletion of Scn1a , resulting in haploinsufficiency, were obtained from the Jackson Laboratory (Jackson Laboratory, ME, USA).

Techniques: Staining, Expressing, Control

Journal: Molecular Therapy Advances

Article Title: Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion

doi: 10.1016/j.omta.2026.201703

Figure Lengend Snippet: CpG depletion does not alter transgene expression but prevents AAV-induced dendritic loss (A) Immunoblot of S1 homogenates probed with antibodies against transgene product EGFP and loading control GAPDH following injection of 1 × 10 10 vg of unmodified AAV1-pCAG-FLEX-EGFP or CpG-depleted AAV1-pCAG-FLEX-EGFP into Slc17a7-IRES2-Cre-D mice. Each lane contains samples from a different animal. UT, untreated. (B) Densitometry shows that EGFP protein levels are indistinguishable in ipsilateral S1 of Slc17a7-IRES2-Cre-D mice injected with either CpG-depleted or unmodified virus. EGFP protein levels are normalized to GAPDH protein levels in the same lane and represented as a fold change from the AAV1-treated condition. (C) Representative cortical neurons from untreated wild-type mice or ipsilateral (injected) hemispheres of wild-type mice injected with 1 × 10 10 vg of either unmodified or CpG-depleted AAV1-pCAG-FLEX-EGFP. Scale bars, 100 μm. (D) Total dendritic length and (E) total Sholl intersections of cortical neurons from untreated wild-type mice and wild-type mice injected with 1 × 10 10 vg of either unmodified or CpG-depleted AAV1-pCAG-FLEX-EGFP. Values are represented as a ratio of injected (ipsi) normalized to uninjected (contra) hemispheres. (F–H) Sholl intersections plotted as a function of distance from the soma for cortical neurons from the same animals shown in (E). (D and E), n = 4 untreated control mice, 10–14 neurons per animal (average = 12 cells); n = 5 mice injected with unmodified AAV1-pCAG-FLEX-EGFP, 10–14 neurons per animal (average = 12 cells); n = 5 mice injected with CpG-depleted AAV1-pCAG-FLEX-EGFP, 12–15 neurons per animal (average = 13 cells). Data in (B and D–H) are represented as mean ± SD. ∗∗∗∗ p < .0001; ∗∗∗ p < .001; ∗∗ p < .01; ns, not significant. In (G), a single ∗ indicates p < 0.05, and vertically stacked ∗ indicate p < 0.01. Statistical analysis: in (B, F–H), two-tailed unpaired t test; in (D) and (E), one-way ANOVA with Tukey’s multiple comparison test.

Article Snippet: Male C57BL/6J and Slc17a7-IRES2-Cre-D (Strain # 037512) mice were obtained from Jackson Laboratory (The Jackson Laboratory, Bar Harbor, ME).

Techniques: Expressing, Western Blot, Control, Injection, Virus, Two Tailed Test, Comparison

Journal: Cell Reports Medicine

Article Title: A dual-adjuvanted HA stem nanoparticle vaccine elicits a multifunctional antibody response that is associated with protection in newborn monkeys

doi: 10.1016/j.xcrm.2026.102746

Figure Lengend Snippet: Conjugation of R848 to H1ssF-Cys nanoparticles (A) Representative image of H1ssF-Cys mutant. (B and C) Size (B) and PDI (C) analysis of H1ssF (WT and Cys mutant) using DLS. (D) Schematic for conjugation of R848 to H1ssF-Cys. BALB/c mice ( n = 3–12 across 3–4 experiments depending on the vaccine tested) were vaccinated and NC99 stem-specific Abs were quantified 14 days p.v. (E) BALB/c mice ( n = 3–12 across 3–4 experiments depending on the vaccine tested) were vaccinated and NC99 stem-specific Abs were quantified 14 days p.v. The dotted line indicates the limit of detection for the assay. TT was defined as the highest dilution with an OD 450 greater than three times the assay background. Lines represent the mean ± SEM. (F) Negatively stained TEM images of the conjugated H1ssF-R848. The scale bar lengths are as follows: 50 nm (A and F, left), 10 nm (F, right). Not significant p ≥ 0.05 (not indicated on graph), ∗∗ p ≤ 0.01, ∗∗∗∗ p ≤ 0.0001.

Article Snippet: Six-week-old female BALB/c (strain code 028) mice were obtained from Charles River Laboratories.

Techniques: Conjugation Assay, Mutagenesis, Staining