| 2. |
- Mcgowan, Asmaa, et al.
(author)
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Injectable Biodegradable Silica Depot for Controlled Subcutaneous Delivery of Antisense Oligonucleotides with beyond Monthly Administration
- 2023
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In: Molecular Pharmaceutics. - : AMER CHEMICAL SOC. - 1543-8384 .- 1543-8392. ; 21:1, s. 143-151
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Journal article (peer-reviewed)abstract
- Single-stranded antisense oligonucleotides (ASOs) are typically administered subcutaneously once per week or monthly. Less frequent dosing would have strong potential to improve patient convenience and increase adherence and thereby for some diseases result in more optimal therapeutic outcomes. Several technologies are available to provide sustained drug release via subcutaneous (SC) administration. ASOs have a high aqueous solubility and require relatively high doses, which limits the options available substantially. In the present work, we show that an innovative biodegradable, nonporous silica-based matrix provides zero-order release in vivo (rats) for at least 4 weeks for compositions with ASO loads of up to about 100 mg/mL (0.5 mL injection) without any sign of initial burst. This implies that administration beyond once monthly can be feasible. For higher drug loads, substantial burst release was observed during the first week. The concentrations of unconjugated ASO levels in the liver were found to be comparable to corresponding bolus doses. Additionally, infusion using a minipump shows a higher liver exposure than SC bolus administration at the same dose level and, in addition, clear mRNA knockdown and circulating protein reduction comparable to SC bolus dosing, hence suggesting productive liver uptake for a slow-release administration.
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| 3. |
- Nordlander, Josefine, et al.
(author)
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Genetic diversity in gooseberry (Ribes uva-crispa), as estimated with SSR markers
- 2022
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In: Scientia Horticulturae. - : Elsevier BV. - 0304-4238 .- 1879-1018. ; 306
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Journal article (peer-reviewed)abstract
- European gooseberry (Ribes uva-crispa L.) is a popular berry crop in many European countries, including Sweden, Denmark and Ukraine. There is no active gooseberry breeding programme in either Sweden or Denmark, but a successful programme is operating in Ukraine. In Sweden and Denmark, research on gooseberries is primarily focused on collection and phenotypic evaluation of genetic resources. As part of these activities, a large number of inventory finds have been collected but have not yet been characterised morphologically or molecularly. The goal of this study was thus to characterise gooseberry germplasm with 15 simple sequence repeat (SSR) markers. From 242 accessions analysed, 153 unique genotypes were identified. Cultivars that have been in widespread cultivation in Sweden, such as the Finnish cultivars ‘Hinnonmäen Keltainen’ and ‘Hinnonmäen Punainen’, had relatively large numbers of synonymous samples. While many inventory finds were identifiable as synonyms of known cultivars, several were found to constitute unique genotypes within the germplasm studied. The studied genotypes clustered relatively well in three posterior groups, consisting of cultivars originating before and after the American gooseberry mildew (Sphaerotheca mors-uvae) outbreak around 1900 and cultivars originating from the territory of the former Soviet Union. A fourth genetic cluster consisting mainly of inventory finds from central and northern Sweden was also identified. In addition, it was possible to verify recorded and stipulated parentages for some of the cultivars studied and to identify three likely parent-parent-child trios. Thus, inventories of local gooseberry germplasm and a subsequent genotyping proved successful in finding unique local genotypes, with potential local adaptation. The data obtained provide a foundation for future studies of gooseberry genetic resources, while also illustrating the importance of a well-curated and phenotypically characterised set of reference cultivars for future studies.
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