mRNA initiation and termination are spatially coordinated.

The expression of a precise mRNA transcriptome is crucial for establishing cell identity and function, with dozens of alternative isoforms produced for a single gene sequence. The regulation of mRNA isoform usage occurs by the coordination of co-transcriptional mRNA processing mechanisms across a gene. Decisions involved in mRNA initiation and termination underlie the largest extent of mRNA isoform diversity, but little is known about any relationships between decisions at both ends of mRNA molecules.

Widespread occurrence of hybrid internal-terminal exons in human transcriptomes.

Messenger RNA isoform differences are predominantly driven by alternative first, internal, and last exons. Despite the importance of classifying exons to understand isoform structure, few tools examine isoform-specific exon usage. We recently observed that alternative transcription start sites often arise near internal exons, often creating “hybrid” first/internal exons.

Engineering exosomes for pulmonary delivery of peptides and drugs to inflammatory lung cells by inhalation.

Exosomes have been investigated as delivery vesicles for various drugs. However, exosome-mediated peptide delivery into the lungs has not been studied. In this study, exosomes were engineered for the pulmonary delivery of RAGE-binding peptide (RBP), an anti-inflammatory peptide.

Brain gene delivery using histidine and arginine-modified dendrimers for ischemic stroke therapy.

Polyamidoamine dendrimer has been studied as an efficient gene carrier. Due to its anti-inflammatory properties, polyamidoamine is a useful gene carrier, especially for inflammatory diseases. However, the commonly used polyamidoamine generation 6 dendrimer (PG6) has higher cytotoxicity than low-molecular weight polyamidoamines, which limits its applications.

Delivery of High Mobility Group Box-1 siRNA Using Brain-Targeting Exosomes for Ischemic Stroke Therapy.

Ischemic strokes are caused by decreased blood flow into the brain, due to narrowed cerebral arteries. In the ischemic brain, high-mobility group box 1 (HMGB1) is released into extracellular spaces and induces inflammatory reactions. In this study, HMGB1 small interfering RNA (siRNA) was delivered into ischemic brains by intravenous administration using rabies virus glycoprotein (RVG) peptide-decorated exosomes.

Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes.

Antisense miRNA oligonucleotides against miR-21 (AMO-21) have a therapeutic potential for treatment of glioblastoma. However, glioblastoma-targeted delivery through systemic injection requires development of an efficient targeting carrier. For this purpose, a glioblastoma-targeting carrier was developed using the T7 peptide and exosomes.

Inhalable Gene Delivery System Using a Cationic RAGE-Antagonist Peptide for Gene Delivery to Inflammatory Lung Cells.

Acute lung injury (ALI) is a severe lung inflammatory disease. In ALI, the receptor for advanced glycation end-products (RAGE) is overexpressed in lung epithelial cells and involved in inflammatory reactions. A previous report showed that a RAGE-antagonist peptide (RAP), from high-mobility group box-1, bound to RAGE and reduced inflammatory reactions.

Combined delivery of curcumin and the heme oxygenase-1 gene using cholesterol-conjugated polyamidoamine for anti-inflammatory therapy in acute lung injury.

Background: Acute lung injury (ALI) is an inflammatory lung disease with a high mortality rate. In this study, combined delivery of the anti-inflammatory compound curcumin and the heme-oxygenase-1 (HO-1) gene using cholesterol-conjugated polyamidoamine was evaluated in a mouse model as a therapeutic option for ALI.

Methods: Curcumin was loaded into cholesterol-conjugated polyamidoamine (PamChol) micelles, and curcumin-loaded PamChol (PamChol-Cur) was then complexed with plasmid DNA (pDNA) through charge interactions.

Self-assembled polymeric micelles for combined delivery of anti-inflammatory gene and drug to the lungs by inhalation.

Acute lung injury (ALI) is a lung inflammatory disease for which pulmonary delivery of drug and gene could be a useful strategy. In this study, cholesterol-conjugated polyamidoamine (PAM-Chol) was synthesized and characterized as a carrier for combined delivery of anti-inflammatory gene and drug into the lungs by inhalation. The PAM-Chol formed self-assembled micelles in an aqueous solution with a critical micelle concentration of 0.

A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model.

A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR-21), which inhibits the expression of pro-apoptotic genes such as phosphatase and tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic effects for glioblastomas. In this study, curcumin was loaded into deoxycholic acid-conjugated polyethylenimine (DP) micelles.

Production and application of HMGB1 derived recombinant RAGE-antagonist peptide for anti-inflammatory therapy in acute lung injury.

Acute lung injury (ALI) is an inflammatory lung disease caused by sepsis, infection, or ischemia-reperfusion. The receptor for advanced glycation end-products (RAGE) signaling pathway plays an important role in ALI. In this study, a novel RAGE-antagonist peptide (RAP) was produced as an inhibitor of the RAGE signaling pathway based on the RAGE-binding domain of high mobility group box-1 (HMGB1).

Combined Delivery of a Lipopolysaccharide-Binding Peptide and the Heme Oxygenase-1 Gene Using Deoxycholic Acid-Conjugated Polyethylenimine for the Treatment of Acute Lung Injury.

A ternary complex comprising plasmid DNA, lipopolysaccharide-binding peptide (LBP), and deoxycholic acid-conjugated polyethylenimine (PEI-DA) is prepared for combinational therapy of acute lung injury (ALI). The LBP is designed as an anti-inflammatory peptide based on the lipopolysaccharide (LPS)-binding domain of HMGB-1. In vitro cytokine assays show that LBP reduces levels of proinflammatory cytokines by inhibiting LPS.

Anti-cancer effect of R3V6 peptide-mediated delivery of an anti-microRNA-21 antisense-oligodeoxynucleotide in a glioblastoma animal model.

MicroRNA-21 (miR-21) expression in glioblastoma inhibits the expression of pro-apoptotic genes, thereby promoting tumor growth. A previous study showed that the amphiphilic R3V6 peptide is an efficient carrier of the anti-miR-21 antisense oligodeoxynucleotide (antisense-ODN) into cells in vitro. In the current study, in vivo delivery of antisense-ODN using the R3V6 peptide was evaluated in a glioblastoma animal model.