Journal: Frontiers in Pharmacology

Article Title: Challenges in Treating Genodermatoses: New Therapies at the Horizon

doi: 10.3389/fphar.2021.746664

Figure Lengend Snippet: New and repurposed drugs for different genodermatoses, based on pathophysiology (ongoing trials mentioned in clinicaltrials.gov with NCT).

Article Snippet: , NCT03605069 , AON targeting exon 73 of COL7A1 RNA in a carbomer-based hydrogel (Q313).

Techniques: Cream, Activation Assay, Over Expression, Protease Inhibitor, Expressing, Activity Assay, Control, Gene Expression

Journal: Frontiers in Pharmacology

Article Title: Challenges in Treating Genodermatoses: New Therapies at the Horizon

doi: 10.3389/fphar.2021.746664

Figure Lengend Snippet: Treatments under investigation aiming to restore protein expression (ongoing trials mentioned in clinicaltrials.gov with NCT)

Article Snippet: , NCT03605069 , AON targeting exon 73 of COL7A1 RNA in a carbomer-based hydrogel (Q313).

Techniques: Expressing, Activity Assay, Immunopeptidomics, Mutagenesis, Protease Inhibitor, Formulation

Journal: Frontiers in Pharmacology

Article Title: Challenges in Treating Genodermatoses: New Therapies at the Horizon

doi: 10.3389/fphar.2021.746664

Figure Lengend Snippet: Cell and gene therapies under investigation for genodermatoses mentioned in clinicaltrials.gov with NCT.

Article Snippet: , NCT03605069 , AON targeting exon 73 of COL7A1 RNA in a carbomer-based hydrogel (Q313).

Techniques: Ex Vivo, Derivative Assay, In Situ, In Vivo, Virus, Plasmid Preparation, Expressing, Generated, Genetically Modified

Journal: Experimental & Molecular Medicine

Article Title: Reversibility and therapeutic feasibility of DNM1L -associated neurodevelopmental disorders

doi: 10.1038/s12276-026-01660-z

Figure Lengend Snippet: a Mutation information and representative MRI images of two patients. The T2 axial view of patient 1 was taken at the age of 3 years and 9 months. The FLAIR axial view of patient 2 was taken at the age of 1 year and 10 months, with increased signal intensity indicating atrophic change. b Cross-species conservation of protein sequences near the mutation residue. c The structure of the DRP1 tetramer (PDB, 4BEJ) shown as a ribbon diagram, with each protomer colored differently. Mutated residues are highlighted as sticks and labeled in a zoom-in box. L650 (UniProt ID, O00429-1) corresponds to L624 in DNM1L isoform 2 (UniProt ID, O00429-3) in the displayed structure. d Perturbation modeling of previously reported (G350R and G362S) and novel (L416P and L650R) DNM1L mutants using FoldX. A, B, C and D represent chain IDs in the tetramer structure, while AB, ABC and ABCD correspond to the dimer, trimer and tetramer, respectively. e Representative images of mitochondrial morphology in human NPCs transfected with DNM1L variants. Red, Mitotracker CMXRos; green, GFP; blue, DAPI. Scale bar, 10 μm. f Quantification of mitochondrial morphology in human NPCs transfected with DNM1L variants. n = 3 with at least 60 cells in each condition analyzed for an independent experiment. g Representative images of peroxisomal morphology in human NPCs transfected with DNM1L variants. Red, PMP70; green, GFP; blue, DAPI. Scale bar, 20 μm. h Quantification of peroxisomal morphology in human NPCs transfected with DNM1L variants. Control, n = 21; wild type, n = 34; G350R, n = 25; L416P, n = 31; L650R, n = 40. Bar graphs indicate mean ± s.e.m. Statistical significance is determined by two-way ANOVA with Tukey’s post hoc test for e and the Kruskal–Wallis test with Dunn’s post hoc test for h . ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Article Snippet: Single-guide (sg)RNA targeting endogenous human DNM1L exon 1 was designed with Synthego online tool (Supplementary Table ).

Techniques: Mutagenesis, Residue, Labeling, Transfection, Control

Journal: Experimental & Molecular Medicine

Article Title: Reversibility and therapeutic feasibility of DNM1L -associated neurodevelopmental disorders

doi: 10.1038/s12276-026-01660-z

Figure Lengend Snippet: a , b , Representative images and quantification of GFP signal in postnatal brain slices electroporated with control vector or DNM1L G350R . IUE timelines are indicated above. Black, GFP. Scale bar, 100 μm. b Quantification of GFP + area ratio (G350R/control) in postnatal brain slices. n = 5. c , d Representative images and quantification of P7 mouse brain sections immunostained for CC3. Black arrows indicate positive cells. Black, CC3. Scale bar, 200 μm. n = 5. e IUE scheme for piggyBac system to label neurons and glia. f , g Representative images and quantification of P7 mouse brain sections electroporated with piggyBac system and immunostained with anti-GFP. Black, GFP. Scale bar, 200 μm. n = 4. Bar plot indicates mean ± s.e.m. Statistical significance is determined by the Kruskal–Wallis test with Dunn’s post hoc test for b , the Mann–Whitney test for d and one-way ANOVA with Dunnett’s post hoc test for g . ** P < 0.01; *** P < 0.001; **** P < 0.0001; n.s., not significant. Panel e created with BioRender.com .

Article Snippet: Single-guide (sg)RNA targeting endogenous human DNM1L exon 1 was designed with Synthego online tool (Supplementary Table ).

Techniques: Control, Plasmid Preparation, MANN-WHITNEY

Journal: Experimental & Molecular Medicine

Article Title: Reversibility and therapeutic feasibility of DNM1L -associated neurodevelopmental disorders

doi: 10.1038/s12276-026-01660-z

Figure Lengend Snippet: a Scheme of RNA sequencing sampling from DNM1L iKO NPCs and differentiated neurons. Cells were treated with DMSO (DNM1L ON ) or DOX (DNM1L OFF ) during culture. b , c Functional enrichment analysis of upregulated and downregulated DEGs between DNM1L OFF and DNM1L ON conditions in NPCs ( b ) and neurons ( c ). The bar color indicates the cluster categories of the GO term. d Representative images of neurospheres immunostained with CC3. Red, CC3; blue, DAPI. Scale bar, 50 μm. e Quantification of neurospheres immunostained with CC3. Control Dox−, n = 22; control Dox+, n = 31; DNM1L iKO Dox−, n = 26; DNM1L iKO Dox+, n = 31. f RRHO analysis. The overlap of gene expression alterations by DNM1 L dysfunction ( x axis, DNM1L OFF versus DNM1L ON ) and by neuronal differentiation ( y axis) was compared. Genes were ordered on the basis of their Wald test statistics (log 2 fold change divided by the standard error of the log 2 fold change). Each point on the plot indicates the significance level of the overlap between the two ranked gene lists. Bar graphs indicate mean ± s.e.m. Statistical significance is determined by Brown–Forsythe and Welch ANOVA with Dunnett’s T3 post hoc test for e . **** P < 0.0001.

Article Snippet: Single-guide (sg)RNA targeting endogenous human DNM1L exon 1 was designed with Synthego online tool (Supplementary Table ).

Techniques: RNA Sequencing, Sampling, Functional Assay, Control, Gene Expression

Journal: Experimental & Molecular Medicine

Article Title: Reversibility and therapeutic feasibility of DNM1L -associated neurodevelopmental disorders

doi: 10.1038/s12276-026-01660-z

Figure Lengend Snippet: a Schematic diagram of rescue conditions. Red arrows indicate DOX treatment during culture. b Heat map of sample-to-sample distances based on variance-stabilized transformation of read count data for total gene expression. The clustering of RNA sequencing samples illustrates the genetic relationships, as indicated by the intensities of the square colors. c Overlapped DEGs between the indicated comparison groups are shown as a Venn diagram. DEGs of each group were identified by comparison with the DNM1L ON group. Restored and persistent DEGs in DNM1L OFF condition are filled with green and pink, respectively. d , e Heat maps (left) and functional enrichment analysis (right) of persistent ( d ) and restored ( e ) DEGs. The color gradient in the heat map represents the Z score. Functional enrichment of upregulated and downregulated genes was shown in separate bar plots. The bar color indicates the cluster categories of the GO term.

Article Snippet: Single-guide (sg)RNA targeting endogenous human DNM1L exon 1 was designed with Synthego online tool (Supplementary Table ).

Techniques: Transformation Assay, Gene Expression, RNA Sequencing, Comparison, Functional Assay

Journal: Experimental & Molecular Medicine

Article Title: Reversibility and therapeutic feasibility of DNM1L -associated neurodevelopmental disorders

doi: 10.1038/s12276-026-01660-z

Figure Lengend Snippet: a Scatter plot presenting reversibility of Reactome pathways, color-coded by keyword and sized by gene set size. The x axis is the percentage of reversible genes among the Reactome pathway gene sets, and the y axis is the difference in the extent of change caused by DNM1L dysfunction and under rescue conditions compared with control, expressed as a Z score. b Heat map of PPAR–PGC1α signaling pathway genes in different conditions. The color gradient represents Z scores. c Scheme of mimicking reversible effects by overexpressing the mitochondrial biogenesis master regulator PPARGC1A . d , e Representative images and quantification of P7 PPARGC1A -coexpressing mouse brain sections immunostained with anti-GFP. Black, GFP. Scale bar, 100 μm. n = 5. f , g Representative images and quantification of mouse primary cortical neurons electroporated with control or DNM1L G350R , treated with DMSO vehicle or bezafibrate. Green, GFP. Scale bar, 50 μm. The viability of mouse primary cortical neurons was compared with the starting point DIV 4. n = 6 from two independent experiments for all conditions. h Scheme of bezafibrate administration during the perinatal period. i , j Representative images of P7 mouse brain sections treated with DMSO vehicle or bezafibrate and immunostained with anti-GFP. Black, GFP. Scale bar, 100 μm. n = 5. Bar graphs indicate mean ± s.e.m. Statistical significance is determined by one-way ANOVA with Tukey’s post hoc test for e and j and two-way ANOVA with Bonferroni’s post hoc test for g . * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. Panels c and h created with BioRender.com .

Article Snippet: Single-guide (sg)RNA targeting endogenous human DNM1L exon 1 was designed with Synthego online tool (Supplementary Table ).

Techniques: Control