In this Account, we review findings from structure function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. Researchers have used robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation fairly chain transfer polymerization (RAFT), and ring-opening metastasis Inhibitors,Modulators,Libraries polymerization (ROMP) to engineer materials that enhance extracellular stability and cellular specificity and decrease toxicity. In addition, we discuss polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release. Finally, we describe promising materials with Inhibitors,Modulators,Libraries a range of in vivo applications from pulmonary gene delivery to DNA vaccines.

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“Polymeric gene delivery vectors Inhibitors,Modulators,Libraries show great potential for the construction of the ideal gene delivery system. These systems harness their ability to incorporate versatile functional traits to overcome most impediments encountered in gene delivery: from the initial complexation to their target-specific release of the therapeutic nucleic acids at the cytosol. Among the numerous multifunctional polymers that have been designed and evaluated as gene delivery vectors, polymers with redox-sensitive (or bioreducible) functional domains have gained great attention in terms of their structural and functional traits. The redox environment plays a pivotal role in sustaining cellular homeostasis and natural redox Inhibitors,Modulators,Libraries potential gradients exist between extra- and intracellular space and between the exterior and interior of subcellular organelles.

In some cases, researchers have designed the polymeric delivery vectors to exploit these gradients. For example, researchers have taken advantage Carfilzomib of the high redox potential gradient between oxidizing extracellular space and the reducing environment of cytosolic compartments by integrating disulfide bonds into the polymer structure. Such polymers retain their cargo in the extracellular space but selectively release the therapeutic nucleic acids in the reducing space within the cytosol. Furthermore, bioreducible polymers form stable complex with nucleic acids, and researchers can fabricate these structures to impart several important features such as site-, timing-, and duration period-specific gene expression. Additionally, the introduction of disulfide bonds within these polymers promotes their biodegradability and limits their cytotoxicity.

Many approaches have demonstrated the versatility of bioreducible gene delivery, selleck bio but the underlying biological rationale of these systems remains poorly understood.