Biologics, Volume 4, Issue 1 (March 2024) – 7 articles

Extracellular vesicles (EVs) encompass a diverse array of cell-derived vesicles, originating either from the endosomal compartment (exosomes) or generated through shedding from the cell membrane. These lipid bilayer nanovesicles carry a diverse cargo consisting of nucleic acids, various macromolecules, and growth factors, capable of being assimilated by nearby or distant cells through biofluids, thereby triggering a wide range of cellular responses. Given their distinctive biological characteristics and crucial roles in intercellular communication, EVs have garnered significant attention, especially concerning potential clinical applications. Inheriting cargo from their parent cells, EVs present promising resources for diverse disease biomarkers. Research elucidating the specific impacts of cargo on target cells has sparked enthusiasm for their therapeutic potential. Compelling evidence indicates that RNA cargo housed within EVs can modulate gene expression and influence cellular functions in recipient cells. However, despite significant progress, numerous aspects of EV biology remain obscure, encompassing selective cargo-loading mechanisms that yield distinct compositions from source cells, variability in size and content, and undisclosed pathways governing uptake and cargo fate in recipient cells. A thorough understanding of core EV mechanisms—such as generation, trafficking, and payload delivery—is essential for their effective clinical utilization. This review explores the current understanding of RNA loading and transportation within EVs, shedding light on the advancements made toward clinical applications. Full article

There is a continuous interest in cannabinoids like Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD). Previous experimental research has described the conversion of CBD to either Δ⁸-THC or Δ⁹-THC, depending on the acid catalyst applied. The use of para-toluene sulfonic acid (pTSA) has led to the formation of Δ⁸-THC, while boron trifluoride etherate (BF₃·Et₂O) has mainly yielded Δ⁹-THC. The enormous difference in product selectivity between these two catalysts was investigated with Molecular Modeling, applying quantum chemical density functional theory. It was found that pTSA leads to fast isomerization of Δ⁹-CBD to Δ⁸-CBD and subsequent ring closure to Δ⁸-THC. BF₃·Et₂O catalysis leads to the formation of tertiary carbenium ions in the transition states, which yield Δ⁹-THC and some iso THC. Under dry conditions in refluxing toluene, it was found that pTSA is predominantly present as a dimer, and only a small fraction is available as monomeric catalyst. Applying the computationally derived activation barriers in transition state theory yielded reaction rates that predicted the amounts of cannabinoids that are in close agreement with the experimental findings from the previous literature. Full article

Thirty-four years ago, the groundbreaking work of John McCafferty and Sir Gregory Winter in developing phage display technology revolutionized the discovery of human antibodies, paving the way for diverse applications. Since then, numerous phage-derived antibodies have been successfully developed and advanced into clinical studies, resulting in the approval of more than a dozen therapeutic antibodies. These antibodies have demonstrated efficacy across a spectrum of medical conditions, ranging from autoimmune diseases to various cancers. In this article, we provide an in-depth review of the development of phage display libraries as powerful platforms for therapeutic antibody discovery, elucidating the intricate procedures involved in antibody development. Additionally, we conduct a review of the current ntibody drugs for cancer treatment that have been developed using the phage display platform. Furthermore, we discuss the challenges inherent in this technology, offering insights into potential solutions to enhance crucial steps and facilitate more efficient drug discovery in the field of phage display technology. Full article

Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function. Full article

The use of medicinal plants for the therapy of diseases of the digestive system, where the Andean peoples developed various forms of administration. The objective is to identify medicinal plants used in the therapy of ailments of the digestive system by the Andean inhabitants of Pampas, Tayacaja, Huancavelica, Peru. Methods: Non-probabilistic sampling, using the “snowball” technique, carrying out semi-structured surveys, allowing information to be collected on the prevalence of ailments or diseases of the digestive system treated with medicinal plants, with inhabitants over 20 years of age participating and using the medicinal plants in the therapy of your digestive system ailments, and exclude those inhabitants who do not comply with it. Results: A total of 16 families, 33 genera, and 34 species are reported, where the families that present the greatest abundance of species are Asteraceae and Lamiaceae. The widely used species are Minthostachys mollis (11.9%), Aloe vera (10.4%), Clinopodium bolivianum (9%), Artemisia absinthium (9%), and Matricaria chamomilla (8.2%). Concluding with the identification of a diversity of medicinal flora, used in the therapy of diseases of the digestive system, such as stomach pain, constipation, gallbladder ailments, gastritis, and gastrointestinal, and liver diseases. Full article

Background: Patients living with chronic obstructive pulmonary disease (COPD) are at risk for lower respiratory tract infections caused by respiratory syncytial virus (RSV). The first RSV vaccines were approved in 2023 for adults ages 60 years and older. The safety and efficacy of the RSV vaccines and their clinical implications in patients living with COPD, apart from composite comorbidity results, are under-reported. Methods: This rapid review aimed to collect and report data pertaining to RSV vaccine safety and efficacy in patients living with COPD. Resources searched included Ovid MEDLINE, EMBASE, International Pharmaceutical Abstracts, published peer-reviewed abstracts, ClinicalTrials.gov, and the United States Food and Drug Administration (FDA) website. Results: Seven records were included: five research manuscripts and two ongoing clinical trials. Patients living with COPD were included in RSV vaccine clinical trials, but outcomes of RSV vaccine safety and efficacy in patients living with COPD were grossly unreported. Conclusions: Future clinical trials of patients living with COPD and subgroup analyses of patients living with COPD within existing studies evaluating RSV vaccine safety and efficacy are necessary to substantiate outcomes in this population. Full article

Arboviruses are a group of viruses that are transmitted by arthropods, such as mosquitoes, and cause significant morbidity and mortality worldwide. Currently, there are only a few options, with restricted use, for effective vaccines against these viruses. However, recent advances in arboviral vaccine development have shown promising innovations that have potential in preclinical and clinical studies. Insect-specific viruses have been explored as a novel vaccine platform that can induce cross-protective immunity against related arboviruses. Nanoparticle-based vaccines have also been developed to enhance the immunogenicity and stability of viral antigens. Additionally, vaccines against mosquito salivary proteins that can modulate the host immune response and interfere with arboviral transmission are being explored. Synonymous recoding, such as random codon shuffling, codon deoptimization, and codon-pair deoptimization, is being investigated as a strategy to attenuate the replication of arboviruses in vertebrate cells, reducing the risk of reverting to wild-type virulence. Finally, mRNA vaccines have been developed to rapidly generate and express viral antigens in the host cells, eliciting robust and durable immune responses. The challenges and opportunities for arboviral vaccine development are outlined, and future directions for research and innovation are discussed. Full article