Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology

Abstract

Due to a series of systemic and intracellular obstacles in nucleic acid (NA) therapy, including fast degradation in blood, renal clearance, poor cellular uptake, and inefficient endosomal escape, NAs may need delivery methods to transport to the cell nucleus or cytosol to be effective. Advanced nanoscale biotechnology-associated strategies, such as controlling the particle size, charge, drug loading, response to environmental signals, or other physical/chemical properties of delivery carriers, have provided great help for the in vivo and in vitro delivery of NA therapeutics. In this review, we introduce the characteristics of different NA modalities and illustrate how advanced nanoscale biotechnology assists NA therapy. The specific features and challenges of various nanocarriers in clinical and preclinical studies are summarized and discussed. With the help of advanced nanoscale biotechnology, some of the major barriers to the development of NA therapy will eventually be overcome in the near future.

Therapeutic siRNA: state of the art

“…Subsequently, LNPs have been increasingly used for siRNA delivery because these vesicles can protect entrapped siRNA from nuclease attack and renal clearance and transport siRNA to targeted tissues and cells. [142][143][144] Canonical siRNA-LNPs comprise similar components, e.g., cationic or ionizable lipids, DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), and cholesterol and polyethylene glycol (PEG) lipids. 145 siRNA-LNPs predominantly accumulate in the liver, spleen and kidney after being intravenously injected.…”

Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics

“…What is more, there have been several reports of repurposing of old drugs but in combination with these innovative aspects of nanomedicines, thus providing a new life to some of these compounds. AuNPs' particular properties provide for additional properties and useful utensils to be applied in stimuli-responsive functions for localized and timely release of cargo, for the thermal heating directed at the ablation of malignant cells and the possibility of high accuracy imaging modalities (e.g., molecular computerized tomography) [149][150][151]. Multifunctional AuNPs carrying TNAs and/or gene editing molecular tools have been mostly evaluated in in vitro models, but several of these concepts have also been proven in vivo.…”

Signaling pathways of nucleic acids for bone healing: A review

“…These drugs are lumasiran, vutrisiran, givosiran, and inclisiran, which are agents against primary hyperoxaluria type 1, transthyretin mediated amyloidosis, acute hepatic porphyria, and hypercholesterolemia, respectively. 1,[28][29][30][31] Like the mentioned siRNAs, there are a huge group of miRNAs and antagomirs that are already identified as remarkably stimulators of osteoblast/osteocytic lineage differentiation, proliferation, and survival. In Table 1, we show the most studied miRNAs and antagomirs in relation to bone signaling pathways, their targets, and their final response to bone turnover.…”

“…NAs are very fragile biomolecules outside the nucleus environment. 1 Thus, NAs are easily destroyed either in blood, by renal clearance, or hydroxylation by ribozymes and deoxyribozymes. This is why NAs need a special mechanism to be delivered into the cells.…”