{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:54:46Z","timestamp":1773392086039,"version":"3.50.1"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2003,6,1]],"date-time":"2003-06-01T00:00:00Z","timestamp":1054425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clinical success of gene therapy based on oligonucleotides (ODNs), ribozymes, RNA and DNA will be greatly dependent on the availability of effective delivery systems. Polycations have gained increasing attention as a non-viral gene delivery vector in the past decades. Significant progress has been made in understanding complex formation between polycations and nucleic acids, entry of the complex into the cells and subsequent entry into the nucleus. Sophisticated molecular architectures of cationic polymers have made the vectors more stable and less susceptible to binding by enzymes or proteins. Incorporation of specific ligands to polycations has resulted in more cell-specific uptake by receptor-mediated mechanisms. However, there are still other barriers limiting the transfection efficiency of polycation gene delivery systems. There is a consensus that polycation-DNA complexes (polyplexes) enter cells via the endocytotic pathway. It is not clearly understood, however, how the polyplexes escape (if they do) from endosomes, how DNA is released from the polyplexes or how the released DNA is expressed. The primary focus of this article is to review various polycation gene delivery systems, which are designed to translocate DNA from endosomes into cytosol. Many polycation gene delivery systems have tried to mimic the mechanisms that viruses use for the endosomal escape. Polycation gene delivery systems are usually coupled with synthetic amphipathic peptides mimicking viral fusogenic peptides, histidine-based gene delivery systems for pH-responsive endosomal escape, polycations with intrinsic endosomolytic activity by the proton sponge mechanism and polyanions to mimic the anionic amphiphilic peptides.<\/jats:p>","DOI":"10.1211\/002235703765951311","type":"journal-article","created":{"date-parts":[[2003,6,19]],"date-time":"2003-06-19T04:53:49Z","timestamp":1055998429000},"page":"721-734","source":"Crossref","is-referenced-by-count":316,"title":["Polycation gene delivery systems: escape from endosomes to cytosol"],"prefix":"10.1093","volume":"55","author":[{"given":"Yong Woo","family":"Cho","sequence":"first","affiliation":[{"name":"Akina Inc., West Lafayette , IN 47906,","place":["USA"]}]},{"given":"Jong-Duk","family":"Kim","sequence":"additional","affiliation":[{"name":"Korea Advanced Institute of Science and Technology, Department of Chemical Engineering , Taejon 305-701,","place":["South Korea"]}]},{"given":"Kinam","family":"Park","sequence":"additional","affiliation":[{"name":"Akina Inc., West Lafayette , IN 47906,","place":["USA"]},{"name":"Purdue University, Departments of Pharmaceutics and Biomedical Engineering , West Lafayette, IN 47907,","place":["USA"]}]}],"member":"286","published-online":{"date-parts":[[2003,6,1]]},"reference":[{"key":"2024103109392219500_cit1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/0092-8674(91)90431-W","article-title":"Cytosolic proteins that specifically bind nuclear location signals are receptors for nuclear import","volume":"66","author":"Adam","year":"1991","journal-title":"Cell"},{"key":"2024103109392219500_cit2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0927-7765(01)00191-6","article-title":"Bi-phasic polycation for the DNA carrier responding to endosomal pH","volume":"22","author":"Asayama","year":"2001","journal-title":"Colloids Surf. 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