| 1. |
- Bost, J. P., et al.
(författare)
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Delivery of Oligonucleotide Therapeutics: Chemical Modifications, Lipid Nanoparticles, and Extracellular Vesicles
- 2021
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Ingår i: Acs Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:9, s. 13993-14021
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Tidskriftsartikel (refereegranskat)abstract
- Oligonucleotides (ONs) comprise a rapidly growing class of therapeutics. In recent years, the list of FDA-approved ON therapies has rapidly expanded. ONs are small (15-30 bp) nucleotide-based therapeutics which are capable of targeting DNA and RNA as well as other biomolecules. ONs can be subdivided into several classes based on their chemical modifications and on the mechanisms of their target interactions. Historically, the largest hindrance to the widespread usage of ON therapeutics has been their inability to effectively internalize into cells and escape from endosomes to reach their molecular targets in the cytosol or nucleus. While cell uptake has been improved, "endosomal escape" remains a significant problem. There are a range of approaches to overcome this, and in this review, we focus on three: altering the chemical structure of the ONs, formulating synthetic, lipid-based nanoparticles to encapsulate the ONs, or biologically loading the ONs into extracellular vesicles. This review provides a background to the design and mode of action of existing FDA-approved ONs. It presents the most common ON classifications and chemical modifications from a fundamental scientific perspective and provides a roadmap of the cellular uptake pathways by which ONs are trafficked. Finally, this review delves into each of the above-mentioned approaches to ON delivery, highlighting the scientific principles behind each and covering recent advances.
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| 2. |
- Jalloh, Mohamed F., et al.
(författare)
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Drivers of COVID-19 policy stringency in 175 countries and territories : COVID-19 cases and deaths, gross domestic products per capita, and health expenditures
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: To understand the associations of COVID-19 cases and deaths with policy stringency globally and regionally.Methods: We modeled the marginal effects of new COVID-19 cases and deaths on policy stringency (scored 0–100) in 175 countries and territories, adjusting for gross domestic product (GDP) per capita and health expenditure (% of GDP). Time periods examined were March–August 2020, September 2020– February 2021, and March–August 2021.Results: Policy response to new cases and deaths was faster and more stringent early in the COVID-19 pandemic (March–August 2020) compared to subsequent periods. New deaths were more strongly associated with stringent policies than new cases. In an average week, 1 new death per 100,000 people was associated with a stringency increase of 2.1 units in March–August 2020, 1.3 units in September 2020–February 2021, and 0.7 units in March–August 2021. New deaths in Africa and the Western Pacific were associated with more stringency than in other regions. Higher health expenditure was associated with less stringent policies. GDP per capita did not have consistent patterns of associations with stringency.Conclusions: Our findings demonstrate the need for enhanced mortality surveillance to ensure policy alignment during health emergencies. Countries that invest less of their GDP in health are inclined to enact stringent policies during health emergencies than countries with more significant health expenditure.
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| 3. |
- Jalloh, Mohamed F., et al.
(författare)
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Drivers of COVID-19 policy stringency in 175 countries and territories : COVID-19 cases and deaths, gross domestic products per capita, and health expenditures
- 2022
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Ingår i: Journal of Global Health. - : International Society of Global Health (ISoGH). - 2047-2978 .- 2047-2986. ; 12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: New data on COVID-19 may influence the stringency of containment policies, but these potential effect are not understood. We aimed to understand the associations of new COVID-19 cases and deaths with policy stringency globally and regionally.Methods: We modelled the marginal effects of new COVID-19 cases and deaths on policy stringency (scored 0-100) in 175 countries and territories, adjusting for gross domestic product (GDP) per capita and health expenditure (% of GDP), and public expenditure on health. The time periods examined were March to August 2020, September 2020 to February 2021, and March to August 2021.Results: Policy response to new cases and deaths was faster and more stringent early in the COVID-19 pandemic (March to August 2020) compared to subsequent periods. New deaths were more strongly associated with stringent policies than new cases. In an average week, one new death per 100 000 people was associated with a stringency increase of 2.1 units in the March to August 2020 period, 1.3 units in the September 2020 to February 2021 period, and 0.7 units in the March to August 2021 period. New deaths in Africa and the Western Pacific were associated with more stringency than in other regions. Higher health expenditure as a percentage of GDP was associated with less stringent policies. Similarly, higher public expenditure on health by governments was mostly associated with less stringency across all three periods. GDP per capita did not have consistent patterns of associations with stringency.Conclusions: The stringency of COVID-19 policies was more strongly associated with new deaths than new cases. Our findings demonstrate the need for enhanced mortality surveillance to ensure policy alignment during health emergencies. Countries that invest less in health or have a lower public expenditure on health may be inclined to enact more stringent policies. This new empirical understanding of COVID-19 policy drivers can help public health officials anticipate and shape policy responses in future health emergencies.
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| 4. |
- Munson, Michael J., et al.
(författare)
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A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery
- 2021
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.
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| 5. |
- Sengeh, P, et al.
(författare)
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Community knowledge, perceptions and practices around COVID-19 in Sierra Leone: a nationwide, cross-sectional survey
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:9, s. e040328-
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Tidskriftsartikel (refereegranskat)abstract
- To assess the public’s knowledge, attitudes and practices about the novel coronavirus in Sierra Leone to inform an evidence-based communication strategy around COVID-19.DesignNationwide, cross-sectional Knowledge, Attitudes and Practices survey.Setting56 randomly selected communities in all 14 districts in Sierra Leone.Participants1253 adults aged 18 years and older of which 52% were men.Main outcome measuresWe calculated proportions of core indicators (awareness, knowledge, risk perception, practices). A composite variable for knowledge (based on seven variables) was created, and categorised into low (0–2 correct), medium (3–4) and high (5–7). Predictors of knowledge were analysed with multilevel ordinal regression models. Associations between information sources, knowledge and two practices (washing hands with soap and avoiding crowds) were analysed using multilevel logistic regression models.ResultsWe found that 75% of the respondents felt at moderate or great risk of contracting coronavirus. A majority (70%) of women did not know you can survive COVID-19, compared with 61% of men. 60% of men and 54% of women had already taken action to avoid infection with the coronavirus, mostly washing hands with soap and water (87%). Radio (73%) was the most used source for COVID-19 information, followed by social media (39%). Having a medium or high level of knowledge was associated with higher odds of washing hands with soap (medium knowledge: adjusted OR (AOR) 2.1, 95% CI 1.0 to 4.4; high knowledge: AOR 4.6, 95% CI 2.1 to 10.2) and avoiding crowds (medium knowledge: AOR 2.0, 95% CI 1.1 to 3.6; high knowledge: AOR 2.3, 95% CI 1.2 to 4.3).ConclusionsThis study shows that in the context of COVID-19 in Sierra Leone, there is a strong association between knowledge and practices. Because the knowledge gap differs between genders, regions, educational levels and age, it is important that messages are specifically targeted to these core audiences.
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