Nucleic Acid Delivery to the Vascular Endothelium

Abstract

This Review examines the state-of-the-art in the delivery of nucleic acid therapies that are directed to the vascular endothelium. First, we review the most important homeostatic functions and properties of the vascular endothelium and summarize the nucleic acid tools that are currently available for gene therapy and nucleic acid delivery. Second, we consider the opportunities available with the endothelium as a therapeutic target and the experimental models that exist to evaluate the potential of those opportunities. Finally, we review the progress to date from investigations that are directly targeting the vascular endothelium: for vascular disease, for peri-transplant therapy, for angiogenic therapies, for pulmonary endothelial disease, and for the blood− brain barrier, ending with a summary of the future outlook in this field.

Repression of rRNA gene transcription by endothelial SPEN deficiency normalizes tumor vasculature via nucleolar stress

“…Moreover, pRNA ASO partially but substantially reversed SPEN deficiency-induced tumor vessel normalization, as shown by increased vessel density and decreased pericyte coverage (Supplemental Figure 9C). Furthermore, we constructed liposome nanoparticles (LNPs) conjugated with cyclo (Arg-Gly-Asp-D-Tyr-Lys) peptide (c(RGDyK)), which targets αvβ3 integrin receptors with high affinity on TECs (54,55). The LNP was loaded with a plasmid expressing pRNA (LNP-pR-NA), which could be taken by TECs and increased pRNA level in TECs after infusion (Figure 10A and Supplemental Figure 9, D biogenesis inhibition on tumor angiogenesis is dose dependent.…”

“…To prepare lipid nanoparticles (Xi’an Ruixi Biological Technology Co. Ltd.) ( 54 , 55 ), 60 mg soybean lecithin, 6 mg N-[1-(2,3-dioleoyloxy)-propyl]-N,N,N-trimethylammonium methyl-sulfate, 1.2 mg 1.2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000] (DSPE-PEG2000), 2.4 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]-c(RGDyK) (DSPE-PEG2000-cRGD), and 3.6 mg cholesterol were dissolved in 2 mL ethanol and transferred to solanum-shaped flask. Plasmids (pcDNA3.1, pcDNA3.1-pRNA [–232 to –1 of mouse rDNA, Genebank BK000964.3], refs.…”

“…Preparation of cationic lipid nanoparticles. To prepare lipid nanoparticles (Xi'an Ruixi Biological Technology Co. Ltd.) (54,55)…”

Potentiation of anti-angiogenic eNOS-siRNA transfection by ultrasound-mediated microbubble destruction in ex vivo rat aortic rings

“…Activation or suppression of a specific gene represents an excellent opportunity to modulate the expression of the associated protein. In addition, use of genome editing tools like CRISPR/Cas9 system can result in permanent depletion of gene expression [ 18 ]. Through RNA interference (RNAi), small regulatory RNAs as siRNA or miRNA suppress RNA translation, also resulting in altered protein expression [ 18 , 19 ].…”

“…In addition, use of genome editing tools like CRISPR/Cas9 system can result in permanent depletion of gene expression [ 18 ]. Through RNA interference (RNAi), small regulatory RNAs as siRNA or miRNA suppress RNA translation, also resulting in altered protein expression [ 18 , 19 ]. However, to achieve effective and improved delivery of gene therapeutics, nucleic acids must successfully transfect the host cells and modify protein transduction.…”