ABSTRACT
Aptamers are capable of binding a wide range of biomolecular targets with high affinity and specificity. It has been widely developed for diagnostic and therapeutic purposes. Because of unique three dimensional structures and cell-membrane penetration, aptamers inhibit virus infection not only through binding specific target, such as the viral envelope, genomic site, enzyme, or other viral components, but also can be connected to each other or with siRNA jointly achieve antiviral activity. Taking human immunodeficiency virus and hepatitis C virus as examples, this paper reviewed the effects and mechanisms of aptamers on disturbing viral infection and replication steps. It may provide an insight to the development of aptamer-based new antiviral drugs.
Subject(s)
Humans , Antiviral Agents , Pharmacology , Aptamers, Nucleotide , Pharmacology , Therapeutic Uses , Genome, Viral , HIV , HIV Reverse Transcriptase , Metabolism , Hepacivirus , Genetics , Macular Degeneration , Drug Therapy , Neoplasms , Drug Therapy , Oligodeoxyribonucleotides , Therapeutic Uses , RNA, Small Interfering , Pharmacology , SELEX Aptamer Technique , Viral Envelope Proteins , Metabolism , Virus ReplicationABSTRACT
Recombinant adeno-associated virus (rAAV) has been widely used as vector for gene therapy. However, the effectiveness of gene therapy based on rAAV needs to be further improved. Enhancement of the transduction efficiency is one of the most important fields for rAAV-based gene therapy. Recent results have showed that the ubiquitin-proteasome system plays an important role in the trafficking of rAAV vector in cytoplasm, and regulation of its function may significantly improve the transduction efficiency of rAAV vector in various types of cells and tissues.
Subject(s)
Animals , Humans , Dependovirus , Genetics , Metabolism , Genetic Vectors , Genetics , Metabolism , Transduction, Genetic , Ubiquitin , MetabolismABSTRACT
RNA interference (RNAi) has been proved as a novel approach for gene therapy. However, RNAi mono-therapy only aims at single gene, it therefore may ultimately fail to cure cancers caused by polygene variation. To overcome the deficiency of RNAi mono-therapy, "combinatorial RNA interference" (coRNAi) was put forward as a new strategy. By co-expressing the inducers of RNAi triggering single or multiple targets directly and other RNA- or protein-based silencers, coRNAi keeps target genes silent, prevents carcinogenic progression and induces apoptosis of tumor cells. This paper mainly reviews the major strategies of coRNAi and their applications in cancer gene therapy.
Subject(s)
Animals , Humans , Apoptosis , Genetic Therapy , Methods , MicroRNAs , Genetics , Neoplasms , Genetics , Pathology , Therapeutics , Oncogenes , RNA Interference , RNA, Small Interfering , Genetics , RNA, Small Nuclear , GeneticsABSTRACT
High mobility group A2 protein (HMGA2), an architectural factor, is highly expressed in various cancer types including lung cancers. It is a candidate target for cancer therapy. RNAi is an effective gene silencing method with low cost and less time-consuming. It is possible to exploit this technology in therapy. Here, 5 siRNAs targeting Hmga2 gene (HMGA2 siRNA1-5) were designed and synthesized. MTT assay, colony formation assay, transwell assay and flow cytometry were used to evaluate the effects of these siRNAs on lung cancer cell lines (NCI-H446 and A549). Results from cell proliferation, clone formation, migration and apoptosis showed that HMGA2 siRNA1, 3, 5 could affect these aspects for both lung cancer cell lines. Among the five siRNAs, HMGA2 siRNA5 showed the greatest inhibition effects. The inhibition effects of HMGA2 siRNA5 are sequence specific and are not due to the induction of interferon response. Taken together, siRNAs targeting Hmga2 gene are potential candidates for lung cancer gene therapy.
Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colony-Forming Units Assay , Gene Silencing , Genetic Therapy , HMGA2 Protein , Genetics , Metabolism , Interferons , Metabolism , Lung Neoplasms , Genetics , Metabolism , Pathology , Point Mutation , RNA, Messenger , Metabolism , RNA, Small Interfering , Genetics , TransfectionABSTRACT
Stem cells use asymmetric and symmetric cell division to generate progeny. Symmetric cell division is defined as the generation of daughter cells that are destined to acquire the same fate. Stem cells divide asymmetrically to generate one daughter with a stem-cell fate and one daughter with different fate. Disruption of the machinery that regulates asymmetric division may be a reason for the generation of cancer. The asymmetric mechanism is maintained by cell polarity factors, cell fate determinants, and the spindle apparatus. The mutation or dysregulation of these factors may change stem cells from asymmetric to symmetric cell division, then leading to tumorigenesis. Therefore, further study is needed on the mechanisms of stem cell control between asymmetric and symmetric cell division, as well as the relationships among stem cells, cancer stem cells, and tumor cells. It may bring us a new approach for the resistance, recurrence, and metastasis of tumors.
Subject(s)
Animals , Humans , Cell Division , Physiology , Cell Polarity , Cell Transformation, Neoplastic , Drosophila , Cell Biology , Neoplasms , Pathology , Neoplastic Stem Cells , Pathology , Neurons , Cell Biology , Spindle Apparatus , Metabolism , Tumor Suppressor Proteins , MetabolismABSTRACT
Gene medicine based on recombinant adeno-associated virus (rAAV) vector has rapidly become the prior-choose reagent for gene therapy, since it had been shown that the rAAV was able to stably express many genes in vivo without detectable side-effect. However, recent findings of CTL immune responses to AAV capsid in a clinical trial highlighted a new issue regarding safety that previously was not identified in animal studies. Obviously it is so important to understand the interaction of rAAV with the immune system in details for the safety and success of rAAV gene medicine. In this review we evaluate several current hypotheses aiming to explain the cellular immunotoxicity, also analysis the current findings including the presentation kinetics of the capsid antigen and the activation of CTL. Focusing on the key steps of the immune response several solutions are proposed, including immunosuppression, optimization of vector and improvement of purity, in order to insure clinical safety and efficacy of rAAV.