Search

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Dilution is a common procedure in biological and chemical analyses to perform tests at different concentrations. In previously reported micro diluters, although they could provide a wide dilution range, only limited dilution ratios were demonstrated, i.e. low flexibility in dilution ratio. Here, a droplet-based micro diluter with high flexibility on dilution ratio is proposed, fabricated, and tested. Through combination of five different electrode sizes using electrowetting-on-dielectric (EWOD) technique, the proposed micro diluter can provide 49 dilution ratios at dilution range from 1/2 to 1/50. Experimental results verify that different dilution ratios can be successfully generated, even at the most difficult low concentration range. Comparing to the design with equal electrode size in conventional EWOD-based microfluidic chip, the proposed design with unequal electrode sizes can reduce the operation steps to achieve high flexibility on dilution ratios efficiently.