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Understanding the Technologies Involved in Gene Therapy
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Manish P. Patel, Jayvadan K. Patel, Mukesh Patel, Govind Vyas
Retroviruses have great potential to go inside in healthy cells and replicate. It has two reprints of a single-stranded RNA genome having gag, pol and env as the sequence. When a virus invades the cell, linear double-stranded DNA forms by reverse transcriptase. At the time of mitosis of the attacked cell, viral DNA integrates with its DNA forming a pro-virus. This pro-viral DNA has been studied for use as retroviral vectors for gene transduction. This pro-viral sequence has the capacity to accommodate and carry the desired gene into the targeted cell. These vectors can also enhance gene expression by CMV promoters. There are three major concerns with the usage of retroviral vectors. First, there is need for gene promoters to express their effect, as in many studies it was found that there is high chance of expression failure in vivo. Second, there is less retroviral titer and finally safety concerns, as retroviruses have the potential to cause various cancers and AIDS, which can be life threatening (Kurian et al. 2000).
Optical Nanosensors
Published in Vinod Kumar Khanna, Nanosensors, 2021
Rev is a vital HIV-1 regulatory protein within the env gene (a gene that encodes a protein precursor for the envelope proteins, found in the retroviral genome) of HIV-1 RNA genome (the entirety of the organism’s hereditary information). The HIV-1 regulatory protein Rev is expressed early in the virus life cycle and thus may be an important target for the immune control of HIV-1 infection and for effective vaccines. Zhang and Johnson (2006) used QDs instead of organic dyes to develop a sensor to determine the dissociation constant (Kd) between Rev and RRE (the Rev response element is a region in the RNA molecule of the HIV env gene), based on FRET. The QDs (emission ~605 nm) were functionalized with streptavidin, a tetrameric protein that binds very tightly to the small molecule, biotin (C10H16N2O3S). The streptavidin-coated QDs functioned as both a nano-scaffold and a FRET donor in this QD-based NS. Streptavidin was bound to biotin-labeled RRE. Nano-scaffolding is a medical process used to regrow tissue and bone, including limbs and organs.
Genome Editing and Gene Therapies: Complex and Expensive Drugs
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
One of the problems associated with attempts to combat viral diseases with genome editing techniques is the creation of escape mutations which holds in particular for CRISPR/Cas-derived mutations. As mentioned elsewhere, DNA double strand breaks are repaired mainly by non-homologous end-joining, an error-prone mechanism leading to insertions and deletions (indels) and investigations into the action of Cas9/5gRNA on HIV-1 DNA have shown that not only new infections are inhibited, but that latent infections are eradicated, too (see, e.g., Hu et al., 2015). Wang et al. (2016) generated CD4+ T cells expressing Cas9/ sgRNA for targeting the overlapping open reading frames of HIV-1 gag/pol and HIV-1 env/ref genes (Subsection 10.4.3.2). All mutations were located in the viral DNA region targeted by these sgRNAs. Some of these mutations turned out to be lethal to the virus. However, other mutations were found to accelerate viral escape as proven by inserting these mutations into the parental viral DNA. Mutations not affecting replication are obviously not recognized by the sgRNA due to respective changes in the DNA sequence. The authors assumed that such indels, compatible with viral viability, are also formed in connection with other Cas9/5gRNA-treated viral diseases.
Gold nanoparticles: a novel paradigm for targeted drug delivery
Published in Inorganic and Nano-Metal Chemistry, 2023
Kamalavarshini S, Ranjani S, Hemalatha S
Nano carrier systems are used to stimulate one's own immune system by injection of killed microbes these modalities as a favorable regime for various infectious diseases and for cancer treatments. This phase of research provides us with positive hope for designing effective vaccines target mediated delivery of varied kinds of immune regulators. Anyways, the efficacy of designed Nano carriers depends upon the appropriate materials used for fabrication, adjuvants, antigens and the other components. Immunoregulations that specifically target antigen suppression are exhibited by Nano vaccines formulations thus extending their abilities for treating auto-immune disorders. Chen et al., researched on multilayered-engineered GNP for playing a role as HIV-1 Env plasmid DNA vaccine for HIV treatment.[30] In the past decade, a diverse portfolio of Nano vaccines having wide range of core or carrier structure materials, their physical and chemical properties, the nature of immune stimulation, their conjugation to various immunomodulatory molecules have been studied and investigated.
A hybrid algorithm for identifying partially conserved regions in multiple sequence alignment
Published in International Journal of Computers and Applications, 2021
Gamage Kokila Kasuni Perera, Champi Thusangi Wannige
For evaluation, we use a data set from an HIV database maintained by Los Alamos National Laboratory [25]. The selected data set is from a study of 11 Swedish patients with a known transmission chain [26]. The data set contains 13 sequences (accession numbers U68496.1 – U68508.1) corresponding to envelope glycoprotein (env) gene, V3 region of the HIV-1 genome. Doctors and nurses with special training in contact tracing have revealed the true transmission history (see Figure 4) using detailed interviews [26].