Therapeutic applications of synthetic gene/genetic circuits: a patent review.

A significant limitation of numerous current genetic engineering therapy approaches is their limited control over the strength, timing, or cellular context of their therapeutic effect. Synthetic gene/genetic circuits are synthetic biology approaches that can control the generation, transformation, or depletion of a specific DNA, RNA, or protein and provide precise control over gene expression and cellular behavior. They can be designed to perform logical operations by carefully selecting promoters, repressors, and other genetic components. Patent search was performed in Espacenet, resulting in 38 selected patents with 15 most frequent international classifications. Patent embodiments were categorized into applications for the delivery of therapeutic molecules, treatment of infectious diseases, treatment of cancer, treatment of bleeding, and treatment of metabolic disorders. The logic gates of selected genetic circuits are described to comprehensively demonstrate their therapeutic applications. Synthetic gene circuits can be customized for precise control of therapeutic interventions, leading to personalized therapies that respond specifically to individual patient needs, enhancing treatment efficacy and minimizing side effects. They can be highly sensitive biosensors that provide real-time therapy by accurate monitoring various biomarkers or pathogens and appropriately synthesizing a therapeutic molecule. Synthetic gene circuits may also lead to the development of advanced regenerative therapies and to implantable biodevices that produce on-demand bioactive molecules. However, this technology faces challenges for commercial profitability. The genetic circuit designs need adjustments for specific applications, and may have disadvantages like toxicity from multiple regulators, homologous recombination, context dependency, resource overuse, and environmental variability.

A patent review of the antimicrobial applications of lectins: Perspectives on therapy of infectious diseases.

Patents of lectins with antiviral, antibacterial and antifungal applications were searched and reviewed. Lectins are proteins that reversibly bind to specific carbohydrates and have the potential for therapy of infectious diseases as biopharmaceuticals, biomedical tools or in drug design. Given the rising concerns over drug resistance and epidemics, our patent review aims to add information, open horizons and indicate our view of the future perspectives about the antimicrobial applications of lectins. Patents with publications until December 2020 were retrieved from Espacenet using defined search terms and Boolean operators. The documents were used to identify the geographical and temporal distribution of the patents, characterize their lectins, and classify and summarize their antiviral, antibiotic and antifungal applications. Lectins are promising antiviral agents against viruses with epidemics and drug resistance concerns. Mannose-binding lectins were the most suggested antiviral agents since glycans with mannose residues are commonly involved in viral entry mechanisms. They were also immobilized onto surfaces to trap viral particles and inhibit their spread and replication. Many patents described the extraction, isolation, amino acid and nucleotide sequences, and expression vectors of lectins with antibiotic and/or antifungal activities in terms of MIC and IC50 for in vitro assays. The inventions also included lectins as biological tools in nanosensors for antibiotics susceptibility tests, drug-delivery systems for the treatment of resistant bacteria, diagnostics of viral diseases and as a vaccine adjuvant. Although research and development of new medicines is highly expensive, antimicrobial lectins may be worth investments given the emergence of epidemics and drug resistance. For this purpose, less invasive routes should be developed as alternatives to the parenteral administration of biologics. While anti-glycan neutralizing antibodies are difficult to develop due to the low immunogenicity of carbohydrates, lectins can be produced more easily and have a broad-spectrum activity. Protein engineering technologies may make the antimicrobial applications of lectins more successful.

The COVID-19 vaccine development: A pandemic paradigm.

COVID-19 pandemic has resulted in millions of deaths and a social-economic crisis. A worldwide effort was made to develop efficient vaccines for this disease. A vaccine should produce immune responses with specific and neutralizing antibodies, and without harmful effects such as the antibody-dependent enhancement that may be associated with severe acute respiratory syndrome. Vaccine design involves the selection of platforms that includes viral, viral-vector, protein, nucleic acid, or trained immunity-based strategies. Its development initiates at a pre-clinical stage, followed by clinical trials when successful. Only if clinical trials show no significant evidence of safety concerns, vaccines can be manufactured, stored, and distributed to immunize the population. So far, regulatory authorities from many countries have approved nine vaccines with phase 3 results. In the current pandemic, a paradigm for the COVID-19 vaccine development has arisen, as many challenges must be overcome. Mass-production and cold-chain storage to immunize large human populations should be feasible and fast, and a combination of different vaccines may boost logistics and immunization. In silico trials is an emerging and innovative field that can be applied to predict and simulate immune, molecular, clinical, and epidemiological outcomes of vaccines to refine, reduce, and partially replace steps in vaccine development. Vaccine-resistant variants of SARS-CoV-2 might emerge, leading to the necessity of updates. A globally fair vaccine distribution system must prevail over vaccine nationalism for the world to return to its pre-pandemic status.

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil.

BACKGROUND: The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE: The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS: DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed. FINDINGS: Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals. MAIN CONCLUSIONS: This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil

BACKGROUND The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses. OBJECTIVE The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil. METHODS DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed. FINDINGS Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals. MAIN CONCLUSIONS This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.