Construction of an Aptamer–SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery

Medicinal Research Reviews

Yang

Tang

2018

129

Gene-based therapy is one of essential therapeutic strategies for precision medicine through targeting specific genes in specific cells of target tissues. However, there still exist many problems that need to be solved, such as safety, stability, selectivity, delivery, as well as immunity. Currently, the key challenges of gene-based therapy for clinical potential applications are the safe and effective nucleic acid drugs as well as their safe and efficient gene delivery systems. In this review, we first focus on current nucleic acid drugs and their formulation in clinical trials and on the market, including antisense oligonucleotide, siRNA, aptamer, and plasmid nucleic acid drugs. Subsequently, we summarize different chemical modifications of nucleic acid drugs as well as their delivery systems for gene-based therapeutics in vivo based on nucleic acid chemistry and nanotechnology methods.

Section: Chemically Modified Nucleic Acid Drugs For Target Specific Imentioning

confidence: 99%

Section: Aptamer-oligonucleotide Conjugatesmentioning

confidence: 99%

Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy

Medicinal Research Reviews

Yang

Tang

2018

129

“…(2) RNA could be specifically and stably delivered to target cells, which can avoid the disadvantages of RNA‐modified TEBVs, including easy degradation and poor targeting. (3) PEI/AuNP was selected as the bridge between TEBV scaffold and exosomes, which can protect exosomes from the high shear blood flow and enhance the stability of TEBV . (4) The exosomes of MSCs with the function of immune privilege and induction of immune tolerance were selected, which might be derived from patient's own cells or allogeneic cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, the inhibition of ADK could protect cell against the damage of pathogenic factors. In the meantime, ADK inhibited cells can sustainably release adenosine which is an optimizing molecule for local microenvironment . EPC capture and antiapoptosis are functions of klotho …”

Section: Introductionmentioning

confidence: 99%

Exosome‐Modified Tissue Engineered Blood Vessel for Endothelial Progenitor Cell Capture and Targeted siRNA Delivery

Macromolecular Bioscience

Yang

Bai

et al. 2017

Self Cite

Instability and poor targeting causes the long-term patency of RNA-modified tissue engineering blood vessels (TEBVs) remaining unsatisfactory. RNA can be enriched in exosome and then delivered into targeted cells while whether exosome-modified TEBVs achieve RNA targeted delivery is unclear. Here, to promote the expression of klotho protein on the mesenchymal stem cell (MSC)-derived exosomes, klotho plasmids are first transfected into MSCs, and adenosine kinase (ADK) siRNA is then loaded into exosome (klotho/ADK siRNA-exosome) using electrotransfection. Flow chamber results show that klotho/ADK siRNA-exosome can effectively capture circulating endothelial progenitor cells (EPCs). Besides, the captured EPCs can endocytose this exosome, and then decompose it into klotho protein and ADK siRNA. Moreover, ADK siRNA promotes the paracrine of proangiogenic factors and adenosine from EPCs, which further facilitate proliferation and migration of endothelial cells. Based on polyethyleneimine-capped gold nanoparticles, exosome-modified TEBVs are constructed through layer-by-layer assembly. Animal experimental results show that klotho/ADK siRNA-exosome-modified TEBVs can maintain the patency up to one month, and good endothelialization is observed. In short, one exosome-modified TEBV is constructed, capture molecules on the surface of exosome capture the circulating EPCs, and the loaded RNA achieves its purpose of accurate treatment depending on the needs of patients.

“…Very recently, using an antiprostate specific membrane antigen aptamer-siRNA chimera, Diao et al (2016) specifically controlled the growth of a prostate tumor. In another interesting study, Chen et al (2015) modified tissue-engineered blood vessels with an aptamer-siRNA chimera and achieved cell-specific delivery and capture. Furthermore, that study showed that PEGylation and 2'fluoro modification of the aptamer increased its stability and specificity.…”

Section: Aptamer-based Chimerasmentioning

confidence: 99%

Cell-targeting aptamers act as intracellular delivery vehicles

Gopinath

Lakshmipriya

Appl Microbiol Biotechnol

et al. 2016

Aptamers are single-stranded nucleic acids or peptides identified from a randomized combinatorial library through specific interaction with the target of interest. Targets can be of any size, from small molecules to whole cells, attesting to the versatility of aptamers for binding a wide range of targets. Aptamers show drug properties that are analogous to antibodies, with high specificity and affinity to their target molecules. Aptamers can penetrate disease-causing microbial and mammalian cells. Generated aptamers that target surface biomarkers act as cell-targeting agents and intracellular delivery vehicles. Within this context, the "cell-internalizing aptamers" are widely investigated via the process of cell uptake with selective binding during in vivo systematic evolution of ligands by exponential enrichment (SELEX) or by cell-internalization SELEX, which targets cell surface antigens to be receptors. These internalizing aptamers are highly preferable for the localization and functional analyses of multiple targets. In this overview, we discuss the ways by which internalizing aptamers are generated and their successful applications. Furthermore, theranostic approaches featuring cell-internalized aptamers are discussed with the purpose of analyzing and diagnosing disease-causing pathogens.