Previous researches utilizing MER proto-oncogene tyrosine kinase (MERTK) gene therapy in Royal College of Surgeons (RCS) rats evidenced its effectiveness in treating MERTK-associated retinitis pigmentosa (RP). Specific ligands for receptor tyrosine kinases, such as growth arrest-specific 6 (Gas6), may enhance retinal phagocytosis via the MERTK receptor, and consequently, enhance the therapeutic effects of gene therapy. In order to overcome the short life effect of the injected Gas6 protein, we constructed a Gas6 loaded methoxy-poly (ethylene glyeol)-poly (lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles (Gas6 NPs) system which allowed for localized and sustained Gas6 protein release, and therefore, a prolonged biological effect. Our data demonstrated that Gas6 protein release from Gas6 NPs preserved the bioactivity and promoted retinal pigment epithelium (RPE) phagocytosis in vitro. In vivo studies showed that RCS rats in the hMERTK/Gas6 NPs group exhibiting the highest electroretinogram responses and more complete retinal structure than that in other groups, further demonstrating that the co-administration of AAV2-BEST1-hMERTK and Gas6 NPs could protect photoreceptors from degeneration. These findings strongly suggest that Gas6 NPs are a promising method to enable the sustained release of Gas6 protein and could therefore enhance the therapeutic effects of gene therapy for MERTK-associated RP.
基金：
This work was supported by National Key R&D Program
of China (2017YFA0104100 and 2016YFC0905201), Beijing
Municipal Institute of Public Medical Research Development
and Reform Pilot Project (2018-2), Beijing Hospitals Authority
Youth Program (QML20180208), and Beijing Institute of
Ophthalmology Key Program (2019003). These funders had no
role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
第一作者机构：[1]Capital Med Univ, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Inst Ophthalmol,Beijing Tongren Eye Ctr, Beijing, Peoples R China[2]Capital Med Univ, Beijing Inst Brain Disorders, Collaborat Innovat Ctr Brain Disorders, Beijing, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Tongren Hosp, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Inst Ophthalmol,Beijing Tongren Eye Ctr, Beijing, Peoples R China[2]Capital Med Univ, Beijing Inst Brain Disorders, Collaborat Innovat Ctr Brain Disorders, Beijing, Peoples R China[3]Capital Med Univ, Beihang Univ, Beijing Tongren Hosp, Beijing Adv Innovat Ctr Big Data Based Precis Med, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Wu Shen,Mao Yingyan,Liu Qian,et al.Sustained Release of Gas6 via mPEG-PLGA Nanoparticles Enhances the Therapeutic Effects of MERTK Gene Therapy in RCS Rats[J].FRONTIERS IN MEDICINE.2021,8:doi:10.3389/fmed.2021.794299.
APA：
Wu, Shen,Mao, Yingyan,Liu, Qian,Yan, Xuejing,Zhang, Jingxue&Wang, Ningli.(2021).Sustained Release of Gas6 via mPEG-PLGA Nanoparticles Enhances the Therapeutic Effects of MERTK Gene Therapy in RCS Rats.FRONTIERS IN MEDICINE,8,
MLA：
Wu, Shen,et al."Sustained Release of Gas6 via mPEG-PLGA Nanoparticles Enhances the Therapeutic Effects of MERTK Gene Therapy in RCS Rats".FRONTIERS IN MEDICINE 8.(2021)
