The large research effort focused on enhancing nonviral transfection vectors has clearly demonstrated that their macromolecular structure has a significant effect on their transfection efficacy. The 3D branched polymeric structures, such as dendrimers, have proved to be a very effective structure for polymeric transfection vectors; however, so far the dendritic polymers have not delivered on their promise. This is largely because a wide range of dendritic polymer materials with tailored multifunctional properties and biocompatibility required for such applications are not yet accessible by current routes. Herein, we report the design and synthesis of new 3D “Single Cyclized” polymeric gene vectors with well-defined compositions and functionalities via a one-step synthesis from readily available vinyl monomers. We observe that this polymer structure of a single chain linked to itself interacts differently with plasmid DNA compared to conventional vectors and when tested over a range of cell types, has a superior transfection profile in terms of both luciferase transfection capability and preservation of cell viability. This new knotted structure shows high potential for gene delivery applications through a combination of simplicity in synthesis, scalability, and high performance.

In multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system, neurodegeneration is detected early in the disease course and is associated with the long-term disability of patients. Neurodegeneration is linked to both inflammation and demyelination, but its exact cause remains unknown. This gap in knowledge contributes to the current lack of treatments for the neurodegenerative phase of MS. Here we ask if neurodegeneration in MS affects specific neuronal components and if it is the result of demyelination. Neuropathological examination of secondary progressive MS motor cortices revealed a selective vulnerability of inhibitory interneurons in MS. The generation of a rodent model of focal subpial cortical demyelination reproduces this selective neurodegeneration providing a new preclinical model for the study of neuroprotective treatments.

A hyperbranched 2-(dimethylamino)ethyl methacrylate (DMAEMA) based polymer has been synthesised by a one-pot in situ deactivation enhanced atom transfer radical polymerisation (DE-ATRP); it exhibits much higher transfection ability than linear poly(DMAEMA) and is comparable to the well known branched poly(ethylene imine) (PEI) and the SuperFect® dendrimer but with lower cytotoxicity.