Journal: Nature Communications

Article Title: Target-stabilized base editors enable robust high-fidelity RNA editing

doi: 10.1038/s41467-026-69835-w

Figure Lengend Snippet: a Schematic showing the installation of a protective mutation into Angptl3 mRNA and assessment of protein secretion to culture medium. b Quantification of conversion rates of codon UAC to UIC. c Western blot analysis of intracellular and secreted Angptl3-HA. d Quantitative analysis of the ratios of secreted Angptl3-HA to either intracellular Angptl3-HA or GAPDH. e Schematic showing RECODEv1 components loaded into rAAVs, and the experimental timeline. The mouse illustration was created in BioRender Liu, T. (2026) https://BioRender.com/2pfrc45 . ADAR1d# denotes P-C4 (F992W). f Heatmap shows editing rates of adenosines in the Angptl3 sequence covered by guides. The adenosines are colored red, with the target adenosine highlighted in bold. g Quantification of editing rates of target adenosine by RECODEv1. h Quantification of serum levels of Angptl3, triglyceride (TG), total cholesterol (T-CHO), ALT, and AST following treatment with RECODEv1. i Histogram shows the body weight of mice following treatment with RECODEv1. j Representative image shows immunoblotting of hepatic Angptl3. GAPDH was used as a loading control. k Quantitative analysis of immunoblot band intensity of Angptl3. l Histogram shows TG content in the liver. For ( b , d ), data are presented as mean ± SEM from 4 biological replicates. Two-tailed unpaired t test: **** p < 0.0001. For ( g – l ), data are presented as mean ± SEM. n = 7 for mice treated by NT gRNA, n = 9 for mice treated by targeting gRNA with UDeg3a-tagged deaminase, n = 9 for mice treated by targeting gRNA with UDeg3b-tagged deaminase. One-way ANOVA: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: Human SOD1, mouse Angptl3, and mNeonGreen were detected by antibody (10269-1-AP, Proteintech), antibody (86193-1-RR, Proteintech), and antibody (29523-1-AP, Proteintech), respectively.

Techniques: Mutagenesis, Western Blot, Sequencing, Control, Two Tailed Test

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: ANGPTL3 is elevated in the diabetic ocular microenvironment. ( A ) Bioinformatics analysis showing an upregulation of ANGPTL3 and ANGPTL4 in aqueous humor. ( B , C ) Western blot analysis of ANGPTL3 and ANGPTL4 in retinal tissue from the DR group and controls. ( D , E ) Immunofluorescence staining for ANGPTL3 in retinal sections from control and STZ-diabetic mice (nuclei counterstained with DAPI)

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques: Western Blot, Immunofluorescence, Staining, Control

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: Genetic targeting of ANGPTL3 rescues diabetic retinal vascular leakage. ( A ) Body weight of the mice. ( B and C ) IPGTT and corresponding AUC. ( D and E ) Representative FFA and quantification of extravascular/intravascular fluorescence intensity ratio. ( F and G ) Representative OCT images and quantification of retinal layer thickness. ( H ) PAS staining of retinal vasculature (scale bar = 50 μm). ( I ) Quantification of AC-Cap, EC, and PC based on PAS-stained images in ( H )

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques: Fluorescence, Staining

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: ANGPTL3 overexpression exacerbates STZ-induced retinal vascular leakage in diabetic mice. ( A ) Plasma ANGPTL3 levels following AAV-mediated ANGPTL3 overexpression. ( B and C ) IPGTT and AUC following ANGPTL3 overexpression. ( D and E ) Representative FFA images and quantification of vascular leakage in ANGPTL3-overexpressing mice. * P < 0.05, ** P < 0.01

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques: Over Expression, Clinical Proteomics

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: ANGPTL3 knockout preserves retinal endothelial barrier function by upregulating tight junction proteins. ( A ) Representative TEM images showing tight junction structures in retinal capillary endothelial cells of control, diabetic, and Angptl3 knockout mice. ( B ) Immunofluorescence staining of retinal sections for tight junction proteins ZO-1 and VE-cadherin. Scale bars = 10 μm. ( C and D ) Quantification of ZO-1 and VE-cadherin fluorescence intensity from ( B ). ( E ) Proliferation assay of HUVECs treated with recombinant human ANGPTL3. ( F ) Western blot analysis of ZO-1 and VE-cadherin protein levels in HUVECs following ANGPTL3 treatment. ( G - H ) Quantification of protein expression from ( F ). * P < 0.05, ** P < 0.01

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques: Knock-Out, Control, Immunofluorescence, Staining, Fluorescence, Proliferation Assay, Recombinant, Western Blot, Expressing

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: ANGPTL3 compromises the endothelial barrier via integrin α5-dependent signaling. ( A ) Protein interaction network analysis. ( B ) Protein docking simulation ( C ) Co-IP assay between integrin α5 and ANGPTL3 in HUVECs. ( D ) Quantification of fluorescence intensity in endothelial permeability. ( E ) Representative immunofluorescence images of HUVECs stained for ZO-1 and VE-cadherin. Scale bars = 20 μm. ( F and G ) Quantification of ZO-1 and VE-cadherin fluorescence intensity is shown in ( E ). * P < 0.05, ** P < 0.01

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques: Co-Immunoprecipitation Assay, Fluorescence, Permeability, Immunofluorescence, Staining

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: Therapeutic targeting of ANGPTL3 with evinacumab rescues retinal vascular leakage without altering systemic metabolism. ( A ) Flowchart of the study. ( B ) Fasting blood glucose level. ( C ) Body weight of the mice. ( D - E ) Representative FFA images and quantification of vascular leakage. * P < 0.05, ** P < 0.01

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques:

Journal: Journal of Translational Medicine

Article Title: The ANGPTL3-integrin α5 axis drives retinal vascular leakage in diabetic retinopathy

doi: 10.1186/s12967-026-07710-4

Figure Lengend Snippet: Schematic of the proposed mechanism for ANGPTL3-mediated BRB disruption in DR. Under diabetic conditions, increased ANGPTL3 interacts with endothelial integrin α5, leading to the downregulation of tight junction proteins (ZO-1, VE-cadherin). This compromises BRB integrity and causes vascular leakage. Both genetic knockout of Angptl3 and local inhibition with evinacumab rescue this phenotype by preserving tight junction structure and function

Article Snippet: To induce systemic ANGPTL3 overexpression, an adeno-associated virus serotype PHP.Eb construc encoding mouse Angptl3 (AAV- Angptl3 ; full name: PHP.Eb-EGFP- Angptl3 ) was generated by OBiO Technology (Shanghai, China).

Techniques: Disruption, Knock-Out, Inhibition, Preserving