As the coronavirus outbreak quickly surges worldwide, many countries are adopting non-therapeutic preventive measures, which include travel bans, remote office activities, country lockdown, and most importantly, social distancing. However, these measures face challenges in Bangladesh, a lower-middle-income economy with one of the world's densest populations. Social distancing is difficult in many areas of the country, and with the minimal resources the country has, it would be extremely challenging to implement the mitigation measures. Mobile sanitization facilities and temporary quarantine sites and healthcare facilities could help mitigate the impact of the pandemic at a local level. A prompt, supportive, and empathic collaboration between the Government, citizens, and health experts, along with international assistance, can enable the country to minimize the impact of the pandemic.

Exon skipping using antisense oligonucleotides (ASOs) has recently proven to be a powerful tool for mRNA splicing modulation. Several exon-skipping ASOs have been approved to treat genetic diseases worldwide. However, a significant challenge is the difficulty in selecting an optimal sequence for exon skipping. The efficacy of ASOs is often unpredictable, because of the numerous factors involved in exon skipping. To address this gap, we have developed a computational method using machine-learning algorithms that factors in many parameters as well as experimental data to design highly effective ASOs for exon skipping. eSkip-Finder (https://eskip-finder.org) is the first web-based resource for helping researchers identify effective exon skipping ASOs. eSkip-Finder features two sections: (i) a predictor of the exon skipping efficacy of novel ASOs and (ii) a database of exon skipping ASOs. The predictor facilitates rapid analysis of a given set of exon/intron sequences and ASO lengths to identify effective ASOs for exon skipping based on a machine learning model trained by experimental data. We confirmed that predictions correlated well with in vitro skipping efficacy of sequences that were not included in the training data. The database enables users to search for ASOs using queries such as gene name, species, and exon number.

Oligonucleotide-based therapies are a promising approach for treating a wide range of hard-to-treat diseases, particularly genetic and rare diseases. These therapies involve the use of short synthetic sequences of DNA or RNA that can modulate gene expression or inhibit proteins through various mechanisms. Despite the potential of these therapies, a significant barrier to their widespread use is the difficulty in ensuring their uptake by target cells/tissues. Strategies to overcome this challenge include cell-penetrating peptide conjugation, chemical modification, nanoparticle formulation, and the use of endogenous vesicles, spherical nucleic acids, and smart material-based delivery vehicles. This article provides an overview of these strategies and their potential for the efficient delivery of oligonucleotide drugs, as well as the safety and toxicity considerations, regulatory requirements, and challenges in translating these therapies from the laboratory to the clinic.

Duchenne muscular dystrophy (DMD) is a life-shortening X-linked genetic disorder characterized by progressive wasting and weakening of muscles in boys. Loss-of-function mutations in the DMD gene, which codes for dystrophin, lead to this disease. The majority of mutations in this gene result in the exclusion of one or more exons from the transcript, eventually causing the remaining exons not to fit together correctly (i.e., out-of-frame mutations). Antisense oligonucleotides, e.g., phosphorodiamidate morpholino oligomers (PMOs), can induce therapeutic exon skipping during pre-mRNA processing to restore the reading frame of the primary transcript of DMD. As a result, truncated but partially functional dystrophin is produced, potentially slowing down the disease progression. Golodirsen is a provisionally approved PMO-based drug for approx. 8% of all DMD patients amenable to exon 53 skipping. This article summarizes golodirsen's pharmacology, efficacy and safety information. It also discusses some controversies that golodirsen met after the approval.

Introduction: This study aimed to assess the prevalence, sociodemographic factors, reproductive consequences, and heritable disease burdens associated with consanguineous marriage (CM) in Bangladesh. Methods: A total of 7,312 families, including 3,694 CM-families, were recruited from 102 locales of 58 districts of Bangladesh. Using a standard questionnaire, we collected medical history and background sociodemographic data of these families. Family history was assessed by pedigree analysis. Fertility, mortality, secondary sex ratio, selection intensity, lethal equivalents were measured using standard methods. Results: The mean prevalence of CM in our studied population was 6.64%. Gross fertility was higher among CM families, as compared to the non-CM families (p < 0.05). The rate of under-5 child (U5) mortality was significantly higher among CM families (16.6%) in comparison with the non-CM families (5.8%) (p < 0.01). We observed a persuasive rise of abortion/miscarriage and U5 mortality rates with the increasing level of inbreeding. The value of lethal equivalents per gamete found elevated for autosomal inheritances as compared to sex-linked inheritance. CM was associated with the incidence of several single-gene and multifactorial diseases, and congenital malformations, including bronchial asthma, hearing defect, heart diseases, sickle cell anemia (p < 0.05). The general attitude and perception toward CM were rather indifferent, and very few people were concerned about its genetic burden. Conclusion: This study highlights the harmful consequences of CM on reproductive behavior and the incidence of hereditary conditions. It essences the need for genetic counseling from premarital to postnatal levels in Bangladesh.

Multiple lines of evidence indicate that the male sex is a significant risk factor for severe disease and mortality due to coronavirus disease 2019 (COVID-19). However, the precise explanation for the discrepancy is currently unclear. Immunologically, the female-biased protection against COVID-19 could presumably be due to a more rapid and robust immune response to viruses exhibited by males. The female hormones, e.g., estrogens and progesterone, may have protective roles against viral infections. In contrast, male hormones, e.g., testosterone, can act oppositely. Besides, the expression of the ACE-2 receptor in the lung and airway lining, which the SARS-CoV-2 uses to enter cells, is more pronounced in males. Estrogen potentially plays a role in downregulating the expression of ACE-2, which could be a plausible biological explanation for the reduced severity of COVID-19 in females. Comorbidities, e.g., cardiovascular diseases, diabetes, and kidney disorders, are considered significant risk factors for severe outcomes in COVID-19. Age-adjusted data shows that males are statistically more predisposed to these morbidities—amplifying risks for males with COVID-19. In addition, many sociocultural factors and gender-constructed behavior of men and women impact exposure to infections and outcomes. In many parts of the world, women are more likely to abide by health regulations, e.g., mask-wearing and handwashing, than men. In contrast, men, in general, are more involved with high-risk behaviors, e.g., smoking and alcohol consumption, and high-risk jobs that require admixing with people, which increases their risk of exposure to the infection. Overall, males and females suffer differently from COVID-19 due to a complex interplay between many biological and sociocultural factors.