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Recombinant DNA Technology and Gene Therapy Using Viruses
Published in Patricia G. Melloy, Viruses and Society, 2023
Viruses do not just cause disease. Naturally or through genetic engineering, viruses can be used to help humans. Genetic engineering, also known as recombinant DNA technology, was developed about 50 years ago as a method to bring together DNA from different organisms. This technology has revolutionized biomedical research, allowing scientists to express any gene of interest in a new organism, including producing recombinant proteins such as human insulin outside of the body. Recombinant DNA technology includes the use of viruses as one type of vector to deliver a gene for expression in a new organism, and these viral vectors have been used in both gene therapy treatments and vaccines, among other applications. Gene therapy treatments involving viral vectors are being used to treat all different kinds of diseases, including cancer. Viral vectors are also used in vaccines, including COVID-19 vaccines. Undoubtedly, viruses will be a part of many therapeutic applications to prevent or treat diseases in the future.
Nanomedicine Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Saima Zulfiqar, Zunaira Naeem, Shahzad Sharif, Ayoub Rashid Ch., M. Zia-Ul-Haq, Marius Moga
Molecular mechanisms followed by viruses evolved with millions of years for entering into cells with chances of survival for a long period of time followed by turning on the defense system, its inhibition and modification mechanisms [1]. When it was realized in 1990 that viruses have the ability to transfer genes with great efficacy, then non-harmful ones were employed for developing “Recombinant Viral vectors” to be used in applications of gene therapy [2–4]. For the improved performance in drug delivery, efforts were made in order to make the viral vectors safer and development of a method following the intrinsic mechanism by viruses according to their capabilities. These efforts resulted in the establishment of nanomedicine in which various nanosystems have the capacity to transfer the genes in the same way as carried out by viruses. Many delivery systems following the molecular mechanism of viruses have been developed in nanomedicine and biomedical fields for the applications of cancer therapy and regenerative medicines [5, 6]. But it is also the fact that nanotechnology does not only focus on “VIROLOGY” for development of the medical field but is also on the front-line for destroying the infectious viruses.
Emerging Pulmonary Delivery Strategies in Gene Therapy: State of the Art and Future Considerations
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Gabriella Costabile, Olivia M. Merkel
A virus is a biological entity that can penetrate into the cell nucleus of the host and exploit the cellular machinery to express its own genetic material and replace it, then spread to other cells. Viral vectors refer to the use of viruses to deliver genetic materials to the cell. They are extremely attractive because of their ability to enter the cells and their nucleus, but also to induce high transduction efficiency and, depending on the type of viruses employed, e.g. retroviruses, provide also transient or long-term gene expression which is currently difficult to accomplish with non-viral methods (Ibraheem et al. 2014). Several kinds of modified “non-aggressive” viruses have been studied to be used as potential vectors Table 15.1.
Study on lipid nanomicelles targeting placenta for the treatment of preeclampsia
Published in Journal of Drug Targeting, 2022
Yang Liu, Qimeng Zhang, Xingli Gao, Tong Wang
Therefore, the main barrier to siRNA therapy is the delivery of siRNA to target cells. Currently, siRNA delivery vectors include viral, non-viral, aptamer and peptide macromolecules to enhance the uptake and silencing of target cells. After injection, the delivery system should avoid renal filtration, phagocyte uptake, serum protein aggregation, and endogenous nuclease degradation in blood circulation to reach the target cells. After passing through the blood vessels, it passes through the extracellular matrix and fibrin, which are dense networks of polysaccharides. This process may cause large molecules to be held up, slowed down or interrupted during transport. After reaching the target cells, it needs to be ingested by endocytosis while remaining intact and active. The poor safety of viral vectors limits their clinical applicability [27]. As for the research on non-viral carriers, nanoparticles, cationic lipids and polymers have been used to encapsulate and successfully improve the efficacy and safety of siRNA therapeutics [28].
The race for a COVID-19 vaccine: where are we up to?
Published in Expert Review of Vaccines, 2022
Md Kamal Hossain, Majid Hassanzadeganroudsari, Jack Feehan, Vasso Apostolopoulos
Viral vectors are a biological technology that has been used in science and medicine since the 1970s. Very recently, this platform has been used to control the Ebola outbreaks. In this technology, the genetic material (DNA) of a viral vector vaccine is carried within a harmless adenovirus, adeno-associated virus, retrovirus, and lentivirus [64]. Vaccine development using this platform has been widely explored. The genome of one virus is used to deliver the antigen of another virus in this platform. This platform has been validated for large-scale commercial production. However, it has some limitations, such as a significant variation in purification methods, leading to inaccurate purity and activity of the vaccines. This platform has been explored for a number of vaccines such as Ebola, Marburg virus, influenza, Chikungunya, Zika, Lassa mammarena virus, Human/Simian immunodeficiency virus, cancers, and many more [65–67]. Currently, approximately 59 candidates using this platform are under investigation for a COVID-19 vaccine. However, viral vectors may trigger the risk factors, including genotoxic events, e.g. inflammation, random insertion disrupting normal genes, activation of proto-oncogenes, and insertional mutagenesis [68].
Novel and emerging therapeutics for genetic epilepsies
Published in Expert Review of Neurotherapeutics, 2021
Ana Pejčić, Slobodan M. Janković, Miralem Đešević, Refet Gojak, Snežana Lukić, Nenad Marković, Miloš Milosavljević
A key element in the causal treatment of genetic epilepsies is the creation of a reliable and safe vector that would transfer target DNA to neurons and provide long-lasting expression of the transgene. Both viral and non-viral vectors are used for these purposes, but they are still far from ideal. Non-viral vectors are less immunogenic, their production is easier, capacity of the transfer is greater, but the transduction efficacy is lower. Viral vectors may have problem with the host’s specific immunity (due to previous exposure), and there is a risk of insertional mutagenicity and residual toxicity. Luckily, new generation of vectors is being developed with better penetration to the brain, larger transgene capacity, and carrying mechanisms to regulate expression. Selective expression of a transgene in affected brain regions is also recently improved by using gene promoters active only in certain cell types, by the creation of many copies of target motifs for microRNAs, which halt expression in normal regions of the brain, and by direct injection of viral vectors in epileptogenic focus. These technological advancements will probably be reflected in the future through an increased number of phase II and phase II clinical trials involving gene therapy.