COSMOS

RNA-based therapy is one of the most promising approaches to treat human diseases. Specifically, the use of short interfering RNA (siRNA) siRNA and microRNA (miRNA) mimics for in vivo RNA interference has immense potential as it directly lowers the expression of the therapeutic target protein. However, there are a number of major roadblocks to the successful implementation of siRNA and other RNA based therapies in the clinic. These include the instability of RNAs in vivo and the difficulty to efficiently deliver the RNA into the target cells. Hence, various innovative approaches have been taken over the years to develop effective RNA delivery methods. These methods include liposome-, polymeric nanoparticle- and peptide-mediated cellular delivery. In a recent innovative study, bioengineered bacterial outer membrane vesicles were used as vehicles for effective delivery of siRNA into cells in vivo.

To date, low transfection efficiency remains the major drawback of polymer based gene delivery. Many cell types including stem cells, fibroblast and neurons are known to be poorly transfected with polymer based gene carriers and the high toxicity severely restrict their utility in gene delivery. Continual efforts are made to identify cellular barriers to efficient transfection as these carriers have low immunogenicity, ease of manufacturing and scalability. Here, we summarize the current status of understanding on uptake mechanism of polymer-DNA complexes (polyplexes), their endosomal escape, cytosolic transport and nuclear entry of pDNA.

Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

Mitochondria are indispensable in cellular functions such as energy production and death execution. They are emerging as intriguing therapeutic target as their dysregulation was found to be monumental in diseases such as neurodegenerative disease, obesity, and cancer etc. Despite tremendous interest being focused on therapeutically intervening mitochondrial function, few mito-active drugs were successfully developed, particularly due to challenges in delivering active compound to this organelle. In this review, effort in utilizing nanotechnology for targeted mitochondrial delivery of compound is expounded based on the nature of the nanomaterial used. The advantage and potential offered are discussed alongside the limitation. Finally the review is concluded with perspectives of the application of nanocarrier in mitochondrial medicine, given the unresolved concern on potential complications.