Non-Viral Gene Therapy in Trabecular Meshwork Cells to Prevent Fibrosis in Minimally Invasive Glaucoma Surgery

The primary cause of failure for minimally invasive glaucoma surgery (MIGS) is fibrosis in the trabecular meshwork (TM) that regulates the outflow of aqueous humour, and no anti-fibrotic drug is available for intraocular use in MIGS. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a promising anti-fibrotic target. This study aims to utilise a novel lipid nanoparticle (LNP) to deliver MRTF-B siRNA into human TM cells and to compare its effects with those observed in human conjunctival fibroblasts (FF). Two LNP formulations were prepared with and without the targeting peptide cΥ, and with an siRNA concentration of 50 nM. We examined the biophysical properties and encapsulation efficiencies of the LNPs, and evaluated the effects of MRTF-B silencing on cell viability, key fibrotic genes expression and cell contractility. Both LNP formulations efficiently silenced MRTF-B gene and were non-cytotoxic in TM and FF cells. The presence of cΥ made the LNPs smaller and more cationic, but had no significant effect on encapsulation efficiency. Both TM and FF cells also showed significantly reduced contractibility after transfection with MRTF-B siRNA LNPs. In TM cells, LNPs with cΥ achieved a greater decrease in contractility compared to LNPs without cΥ. In conclusion, we demonstrate that the novel CL4H6-LNPs are able to safely and effectively deliver MRTF-B siRNA into human TM cells. LNPs can serve as a promising non-viral gene therapy to prevent fibrosis in MIGS

Recent Advances in Targeted Genetic Medicines for Cystic Fibrosis

The cystic fibrosis transmembrane conductance regulator (CFTR) gene was discovered just over 30 years ago, and soon after, gene therapy for cystic fibrosis (CF) has been rapidly and continually developing. Recently, novel gene therapy strategies have been developed, including mRNA delivery, genome editing, and mRNA repair; all these strategies are collectively named “genetic medicines.” The last quarter of the century showed a significant boost in the development of viral and nonviral vectors to deliver genetic treatment. This chapter will provide a brief overview of the CFTR gene and its different classes of mutations as well as a review of the different genetic therapeutic options that are under research. Later in this chapter, drugs that target different CFTR mutation classes and are currently approved to treat CF patients will be briefly presented

PID Controller tuning and implementation aspects for building thermal control

Δημοσίευση σε επιστημονικό περιοδικόSummarization: The control of the indoor environmental parameters of buildings is an open problem with many practical difficulties which stem from the non-linear, multivariable nature of the building models. This paper presents the tuning process of a conventional PID controller for the thermal comfort control application, in buildings utilizing fieldbus systems. The PID controller has been chosen taking into account its widespread deployment and its attractive features like low computational cost and simplicity of implementation. On the contrary, there is no standard methodology for the extraction of its parameters. Therefore, empirical methods should be utilized along with trial and error techniques on the target application. The design procedure is illustrated and there is special focus regarding the practical aspects of the implementation on a laboratory installation. Finally, the results of the monitored and computed variables of the experimental procedure are presented along with relevant conclusions and discussion.Presented on: WSEAS Transactions on Circuits and System

PID controller tunning and implementation aspects for building thermal control

Summarization: The control of the indoor environmental parameters of buildings is an open problem with many practical difficulties which stem from the non-linear, multivariable nature of the building models. This paper presents the tuning process of a conventional PID controller for the thermal comfort control application, in buildings utilizing fieldbus systems. The PID controller has been chosen taking into account its widespread deployment and its attractive features like low computational cost and simplicity of implementation. On the contrary, there is no standard methodology for the extraction of its parameters. Therefore, empirical methods should be utilized along with trial and error techniques on the target application. The design procedure is illustrated and there is special focus regarding the practical aspects of the implementation on a laboratory installation. Finally, the results of the monitored and computed variables of the experimental procedure are presented along with relevant conclusions and discussion.Presented on: WSEAS Transactions on Circuits and System