Over the past two decades, gene therapy, as a promising way to regulate or replace abnormal gene, has made impressive progress with numerous clinic trials. However, the success of gene therapy was hugely limited by its low translocation into cytoplasm. Therefore, technologies to efficiently protect and deliver therapeutic nucleic acids have been extensively investigated, but most of the delivery strategies involve endosomal entrapment, leading to low delivery efficiency. In this review, we discuss the latest advances in nonendocytosis-dependent strategies for delivering nucleic acids into cells. A highlight is provided on the cellular uptake systems facilitated by the endosome−Golgi−endoplasmic reticulum pathway, pH low insertion peptides, cell-penetrating peptides, scavenger receptor-mediated nonendocytosis, membrane fusion, and the emerged thiol−disulfide exchange. The mechanisms, pros, and cons of these systems are discussed. Finally, current challenges and future perspectives for the translation of nonendocytic gene delivery vectors, especially thiol-mediated cellular uptake, into clinical applications are discussed.
Antibody drugs have been used to treat many diseases, and to date, this has been the most rapidly growing drug class. However, the lack of suitable methods for real-time and highthroughput monitoring of antibody production and quality control has been a hindrance to the further advancement of antibody drugs or biosimilars. Therefore, we herein report a versatile tool for one-step fluorescence monitoring of antibody production by using aptamer probes selected through the in vitro SELEX method. In this case, DNA aptamers were selected against the humanized IgG1 antibody drug trastuzumab with high specificity and affinity with a K d value of aptamer CH1S-3 of 10.3 nM. More importantly, the obtained aptamers were able to distinguish native from heat-treated, whereas antibodies failed this test. On the basis of the advantages of rapid detection for aptamers, we designed aptamer molecular beacons for direct and sensitive detection of trastuzumab in complex samples. Unlike traditional antibody-based ELISA, the signal was observed directly upon interaction with the target without the need for time-consuming binding and multiple washing steps. To further highlight biomedical applications, the use of aptamers as potential tools for quality control and traceless purification of antibody drugs was also demonstrated. Thus, aptamers are shown to be promising alternatives for antibody production monitoring, quality control, and purification, providing technical support to accelerate antibody drug development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.