ABSTRACT
Gene silencing therapies have successfully suppressed the translation of target proteins, a strategy that holds great promise for the treatment of central nervous system (CNS) disorders. Advances in the current knowledge on multimolecular delivery vehicles are concentrated on overcoming the difficulties in delivery of small interfering (si)RNA to target tissues, which include anatomical accessibility, slow diffusion, safety concerns, and the requirement for specific cell uptake within the unique environment of the CNS. The present work addressed these challenges through the implementation of polyornithine derivatives in the construction of polyplexes used as non-viral siRNA delivery vectors. Physicochemical and biological characterization revealed biodegradability and biocompatibility of our polyornithine-based system and the ability to silence gene expression in primary oligodendrocyte progenitor cells (OPCs) effectively. In summary, the well-defined properties and neurological compatibility of this polypeptide-based platform highlight its potential utility in the treatment of CNS disorders.
Subject(s)
Central Nervous System Diseases/therapy , Gene Silencing , Oligodendroglia/metabolism , Peptides , RNA, Small Interfering , Stem Cells/metabolism , Cell Line, Tumor , Central Nervous System Diseases/genetics , Central Nervous System Diseases/metabolism , Central Nervous System Diseases/pathology , Humans , Oligodendroglia/pathology , Peptides/chemistry , Peptides/pharmacology , RNA, Small Interfering/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Stem Cells/pathologyABSTRACT
Procedural variations affecting the reliability of the Mini-Mental State (MMS) were investigated in three studies using three different populations. Consistent results were obtained from studies of neurologically normal, at-risk, and impaired individuals which show that the test item involving serial subtractions is significantly more difficult than the alternative item involving backward spelling. MMS users are cautioned against assuming the comparability of scores across individuals, and should specify which attention and concentration task they employ in their evaluations.
