Nanoparticle for delivery of antisense γPNA oligomers targeting CCR5 (original) (raw)

human peripheral blood mononuclear cells and (2) difficulty in intracellular delivery. In attempts to resolve these limitations, strides have been made by incorporation of numerous cationic residues, 11 inclusion of polar groups in the backbone 12 and nucleobases, 13 and conjugation of high molecular weight polyethylene glycol (PEG) to one of the termini. 14 Though these chemical modifications have led to improvements in solubility and cellular uptake properties, it is often achieved at the expense of binding affinity and sequence specificity. These limitations can be addressed by inducing chirality at the gamma position of regular PNA: one class of chiral PNA is known as gamma PNA (γPNA). Biophysical characterization and NMR structural studies have shown that installation of a chiral center at the gamma position pre-organizes the PNA oligomer and also increases the binding affinity to the cDNA or RNA sequences. 15-20 Recently, by performing a series of thermodynamic studies, we have revealed that inclusion of diethylene glycol at the gamma position (also known as miniPEG-based γPNA) increases the solubility properties of PNA and enhances its binding with cDNA and RNA strands. 17 In addition, we have also shown that mini-PEG-based gamma PNA (MP γPNA) has the potential to invade duplex DNA in a sequence-unrestricted manner. 21 However, more effective intracellular delivery methods are required for broader impact of new generations of gamma PNA in gene therapy-based applications. Recently, we have developed new methods for delivery of PNAs for gene silencing and gene editing. McNeer et al. demonstrated the use of poly(lactide-co-glycolide) (PLGA) nanoparticles for ©2013 Landes Bioscience. Do not distribute.