Omics · study · 2026
Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration
Listed in NCBI GEO
Antisense oligonucleotides (ASOs) are RNA targeting therapies with substantial potential for the medical treatment of genetically defined inherited ocular conditions and beyond.
Description
The eye is, in principle an ideal model for ASO therapeutic development due to the ease of administration and potential limited dosing frequency due to ASO durability. Autosomal dominant drusen (ADD) is an inherited retinal dystrophy characterized by early onset formation of numerous drusen with subsequent choroidal neovascularization (CNV).
ADD is caused by a mutation in the epidermal growth factor-containing fibrillin-like extracellular matrix protein 1 (EFEMP1). EFEMP1R345W is expressed at high levels in the retinal pigmented epithelium (RPE) and accumulates both intracellularly and in the extracellular matrix (ECM) of the RPE during ADD. Furthermore, EFEMP1 has been reported to be significantly upregulated in serum and RPE/choroid during age-related macular degeneration (AMD) yet the consequence of EFEMP1 overexpression has not been fully elucidated.
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Here, we report the development of a biallelic EFEMP1 targeted ASO that has shown robust EFEMP1 knockdown and modulation of disease relevant factors in induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE), human microvascular retinal endothelial cells (HMREC), ex vivo human choroidal explants and in vivo mouse models. We further demonstrate that EFEMP1 is upregulated at the protein level during AMD.
Herein, we report that EFEMP1 knockdown reduces complement factor 3 (C3) levels, a current target for AMD, and significantly reduces proliferation and migration in HMREC and a human choroidal explant sprouting. In summary, we propose a EFEMP1 targeted ASO as a therapeutic modality for DHRD and AMD.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE289nnn/GSE289976 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE289976 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1225679 ncbi.nlm.nih.gov/bioproject/PRJNA1225679 ↗
project · from NCBI GEO
- PubMed 42597498 pubmed.ncbi.nlm.nih.gov/42597498 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE289976 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |