Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers. However, efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging. Recently, more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating. Due to the flexibility and deformability of nucleic acids, the nanoassemblies could be fabricated with different shapes and structures. With hybridization, nucleic acid nanoassemblies, including DNA and RNA nanostructures, can be applied to enhance RNA therapeutics and diagnosis. This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.

Lipid nanomaterials-based RNA therapy and cancer treatment

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

The tumor therapeutic potential of long non-coding RNA delivery and targeting

Long non-coding RNAs (lncRNAs) is a type of RNA over 200 nt long without any protein coding ability, which has been investigated relating to crucial biological function in cells. There are many key lncRNAs in tumor/normal cells that serve as a biological marker or a new target for tumor treatment. However, compared to some small non-coding RNA, lncRNA-based drugs are limited in clinical application. Different from other non-coding RNA, like microRNAs, most lncRNAs have a high molecular weight and conserved secondary structure, making the delivery of lncRNAs more complex than the small non-coding RNAs. Considering that lncRNAs constitute the most abundant part of the mammalian genome, it is critical to further explore lncRNA delivery and the subsequent functional studies for potential clinical application. In this review, we will discuss the function and mechanism of lncRNAs in diseases, especially cancer, and different approaches for lncRNA transfection using multiple biomaterials.

Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis

With the understanding of microRNA (miRNA or miR) functions in tumor initiation, progression, and metastasis, efforts are underway to develop new miRNA-based therapies. Very recently, we demonstrated effectiveness of a novel humanized bioengineered miR-124-3p prodrug in controlling spontaneous lung metastasis in mouse models. This study was to investigate the molecular and cellular mechanisms by which miR-124-3p controls tumor metastasis. Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3p in A549 cells, which were assembled into multiple cellular components critical for metastatic potential. Among them, plectin (PLEC) was verified as a new direct target for miR-124-3p that links cytoskeleton components and junctions. In miR-124-3p-treated lung cancer and osteosarcoma cells, protein levels of vimentin, talin 1 (TLN1), integrin beta-1 (ITGB1), IQ motif containing GTPase activating protein 1 (IQGAP1), cadherin 2 or N-cadherin (CDH2), and junctional adhesion molecule A (F11R or JAMA or JAM1) decreased, causing remodeling of cytoskeletons and disruption of cell-cell junctions. Furthermore, miR-124-3p sharply suppressed the formation of focal adhesion plaques, leading to reduced cell adhesion capacity. Additionally, efficacy and safety of biologic miR-124-3p therapy was established in an aggressive experimental metastasis mouse model

New Directions In Genetic Therapy Research.

Gene therapy involves transfer of normal healthy genes in patients to replace abnormal genes. In several human diseases such as cystic fibrosis, HIV infection, Duchenne's muscular dystrophy, Gaucher disease, arthritis, and cancer, gene therapy has been applied with encouraging success. Unfortunately, side effects are showing up, especially the response of host immune system. New directions in gene therapy research are being pursued to resolve these problems. An example of one such problem is the retrovirus gene delivery system. Since retroviruses grow only in dividing cells and integrated into the host genome in a random manner, the risk of tumor formatting increases. A denovirus can infect nondivinding cells but its titer is very low and it also provokes host immune system response. One the other hand, adeno-associated viruses (AAV) and Herpes simplex viruses, with deleted EI gene, which renders them replication defective can be directly injected into the patients or mixed with cells from the patients just prior to rein fusion. The AAV gene delivery system is (i) stable upon storage at room temperature, (ii) is not inactivated by components in the blood when directly injected into the patients and (iii) does not require specific cells for replication and very efficiently transfers genes into the host target cell DNA. The next vector of choice is cationic liposomes which are neither toxic nor causes cancer in cells. In cystic fibrosis, cationic liposomes have already been tried in the initial phase. The last technique which has been tried at least in 3 human trials is naked or particle meditated DNA injection. It suffers from low target ability and low efficiency effect,. Proposal of synthetic 25 the human chromosome has also been made. In this chromosomal vector not only the c DNA but also the regulatory sequences can also be introduced. In summary, the future of genetic therapy lies on the improvement of the delivery system of normal gene(s) into patients.