An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F21%3A00119123" target="_blank" >RIV/00216224:14110/21:00119123 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985904:_____/21:00543675 RIV/00159816:_____/21:00075196 RIV/00216305:26620/21:PU141849

Výsledek na webu

<a href="https://stm.sciencemag.org/content/13/592/eaba4226" target="_blank" >https://stm.sciencemag.org/content/13/592/eaba4226</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1126/scitranslmed.aba4226" target="_blank" >10.1126/scitranslmed.aba4226</a>

Jazyk výsledku

angličtina

Název v původním jazyce

An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice

Popis výsledku v původním jazyce

Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias.

Název v anglickém jazyce

An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice

Popis výsledku anglicky

Achondroplasia is the most prevalent genetic form of dwarfism in humans and is caused by activating mutations in FGFR3 tyrosine kinase. The clinical need for a safe and effective inhibitor of FGFR3 is unmet, leaving achondroplasia currently incurable. Here, we evaluated RBM-007, an RNA aptamer previously developed to neutralize the FGFR3 ligand FGF2, for its activity against FGFR3. In cultured rat chondrocytes or mouse embryonal tibia organ culture, RBM-007 rescued the proliferation arrest, degradation of cartilaginous extracellular matrix, premature senescence, and impaired hypertrophic differentiation induced by FGFR3 signaling. In cartilage xenografts derived from induced pluripotent stem cells from individuals with achondroplasia, RBM-007 rescued impaired chondrocyte differentiation and maturation. When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Science Translational Medicine

ISSN

1946-6234

e-ISSN

1946-6242

Svazek periodika

13

Číslo periodika v rámci svazku

592

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

„eaba4226“

Kód UT WoS článku

000648584600002

EID výsledku v databázi Scopus

2-s2.0-85105526279