ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Targeted Knockout of the Vegfa Gene in the Retina by Subretinal Injection of RNP Complexes Containing Cas9 Protein and Modified sgRNAs.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Heterogeneous nuclear ribonucleoprotein K in cancer biology and its therapeutic applications (Review).Molecular medicine reports · 2026Review
- AAV-mediated multiple gene therapy combining VEGFA-targeting miR-agshRNAs and PEDF for the suppression of choroidal neovascularization.Molecular therapy. Nucleic acids · 2026Article
- Article
- Dynamically covalent lipid nanoparticles mediate CRISPR-Cas9 genome editing against choroidal neovascularization in mice.Science advances · 2025Article
- Co-delivery of antioxidants and siRNA-VEGF: promising treatment for age-related macular degeneration.Drug delivery and translational research · 2025Review
- Customizable virus-like particles deliver CRISPR-Cas9 ribonucleoprotein for effective ocular neovascular and Huntington's disease gene therapy.Nature nanotechnology · 2025Article
- Review
- Direct delivery of Cas9 or base editor protein and guide RNA complex enables genome editing in the retina.Molecular therapy. Nucleic acids · 2024Article
- Targeted nonviral delivery of genome editors in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy.Acta pharmaceutica Sinica. B · 2024Article
- How Advanced are Nanocarriers for Effective Subretinal Injection?International journal of nanomedicine · 2024Review
- Fire Burn and Cauldron Bubble: What Is in Your Genome Editing Brew?Biochemistry · 2023Review
- Design of Liposome Formulations for CRISPR/Cas9 Enzyme Immobilization: Evaluation of 5-Alpha-Reductase Enzyme Knockout for Androgenic Disorders.ACS omega · 2023Article
- Engineered lentivirus-derived nanoparticles (LVNPs) for delivery of CRISPR/Cas ribonucleoprotein complexes supporting base editing, prime editing and in vivo gene modification.Nucleic acids research · 2023Article
- Bioinformatic and literature assessment of toxicity and allergenicity of a CRISPR-Cas9 engineered gene drive to control Anopheles gambiae the mosquito vector of human malaria.Malaria journal · 2023Article
- Poly (β-amino Ester) Nanoparticles Modified with a Rabies Virus-derived peptide for the Delivery ofACS applied nano materials · 2023Article
- CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization.Scientific reports · 2023Article
- Clinical progress in genome-editing technology and in vivo delivery techniques.Trends in genetics : TIG · 2023Review
- Novel Approaches in the Drug Development and Delivery Systems for Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2023Review
- Adeno-Associated Virus (AAV) - Based Gene Therapies for Retinal Diseases: Where are We?The application of clinical genetics · 2023Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic effect of retinal gene therapy using CRISPR/Cas9-mediated genome editing and knockout applications is dependent on efficient and safe delivery of gene-modifying tool kits. Recently, transient administration of single guide RNAs (sgRNAs) and SpCas9 proteins delivered as ribonucleoproteins (RNPs) has provided potent gene knockout in vitro. To improve efficacy of CRISPR-based gene therapy, we delivered RNPs containing SpCas9 protein complexed to chemically modified sgRNAs (msgRNAs). In K562 cells, msgRNAs significantly increased the insertion/deletion (indel) frequency (25%) compared with unmodified counterparts leading to robust knockout of the VEGFA gene encoding vascular endothelial growth factor A (96% indels). Likewise, in HEK293 cells, lipoplexes containing varying amounts of RNP and EGFP mRNA showed efficient VEGFA knockout (43% indels) and strong EGFP expression, indicative of efficacious functional knockout using small amounts of RNP. In mice, subretinal injections of equivalent lipoplexes yielded 6% indels in Vegfa of isolated EGFP-positive RPE cells. However, signs of toxicity following delivery of lipoplexes containing high amounts of RNP were observed. Although the mechanism resulting in the varying efficacy remains to be elucidated, our data suggest that a single subretinal injection of RNPs carrying msgRNAs and SpCas9 induces targeted retinal indel formation, thus providing a clinically relevant strategy relying on nonviral delivery of short-lived nuclease activity.
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