Manufacturing Challenges and Rational Formulation Development for AAV Viral Vectors

Journal of Pharmaceutical Sciences, Journal Year: 2021, Volume and Issue: 110(7), P. 2609 - 2624

Published: April 2, 2021

Adeno-associated virus (AAV) has emerged as a leading platform for gene delivery treating various diseases due to its excellent safety profile and efficient transduction target tissues. However, the large-scale production long-term storage of viral vectors is not resulting in lower yields, moderate purity, shorter shelf-life compared recombinant protein therapeutics. This review provides comprehensive analysis upstream, downstream formulation unit operation challenges encountered during AAV vector manufacturing, discusses how desired product quality attributes can be maintained throughout by understanding degradation mechanisms strategies. The physical chemical instabilities that may encounter because stressed conditions such thermal, shear, freeze-thaw, light exposure are highlighted. role buffer, pH, excipients, impurities on stability also discussed. As such, aim this outline tools potential roadmap improving AAV-based drug products stressing need mechanistic involved processes.

Language: Английский

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Negative emissions and the long history of carbon removal

Wiley Interdisciplinary Reviews Climate Change, Journal Year: 2020, Volume and Issue: 11(6)

Published: Aug. 27, 2020

Abstract Recent IPCC assessments highlight a key role for large‐scale carbon removal in meeting the objectives of Paris Agreement. This focus on removal, also referred to as negative emissions, is suggestive novel opportunities, risks, and challenges addressing climate change, but tends build narrow techno‐economic framings that characterize integrated assessment modeling. While discussion emissions bears important parallels wider older literature sequestration sinks, this earlier scholarship—particularly from critical social sciences—is seldom engaged with by research community. In article, we survey “long history” seek draw out lessons ongoing emerging public debate emissions. We argue policy should proceed not just projections future, an acknowledgement past controversies, successes failures. particular, our review calls attention irreducibly political character imaginaries accounting practices urges experiences implementation (small‐scale) projects. Our way highlights importance seeing continuity more engagement existing science scholarship subject. Acknowledging embracing interdisciplinary agenda are aspects making change mitigation responsible, precondition avoid repeating mistakes article categorized under: The Carbon Economy Climate Mitigation > Benefits

Language: Английский

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Alternative Biome States in Terrestrial Ecosystems

Trends in Plant Science, Journal Year: 2020, Volume and Issue: 25(3), P. 250 - 263

Published: Jan. 6, 2020

Language: Английский

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Integrated global assessment of the natural forest carbon potential

Nature, Journal Year: 2023, Volume and Issue: 624(7990), P. 92 - 101

Published: Nov. 13, 2023

Abstract Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1 . Remote-sensing estimates to quantify losses from global forests 2–5 characterized by considerable uncertainty we lack comprehensive ground-sourced evaluation benchmark these estimates. Here combine several 6 satellite-derived approaches 2,7,8 evaluate forest potential outside agricultural urban lands. Despite regional variation, predictions demonstrated remarkable consistency at scale, with only 12% difference between At present, storage is markedly under natural potential, total deficit 226 Gt (model range = 151–363 Gt) areas low human footprint. Most (61%, 139 C) existing forests, which ecosystem protection can allow recover maturity. The remaining 39% (87 lies regions been removed or fragmented. Although cannot be substitute for emissions reductions, our results support idea 2,3,9 that conservation, restoration sustainable management diverse offer valuable contributions meeting biodiversity targets.

Language: Английский

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Wildfire and climate change adaptation of western North American forests: a case for intentional management

Ecological Applications, Journal Year: 2021, Volume and Issue: 31(8)

Published: Aug. 2, 2021

Forest landscapes across western North America (wNA) have experienced extensive changes over the last two centuries, while climatic warming has become a global reality four decades. Resulting interactions between historical increases in forested area and density recent rapid warming, increasing insect mortality, wildfire burned areas, are now leading to substantial abrupt landscape alterations. These outcomes forcing forest planners managers identify strategies that can modify future ecologically and/or socially undesirable. Past management, including widespread harvest of fire- climate-tolerant large old trees forests, fire exclusion (both Indigenous lightning ignitions), highly effective suppression contributed current state wNA forests. practices were successful at meeting short-term demands, but they match poorly modern realities. Hagmann et al. review century observations multi-scale, multi-proxy, research evidence details regimes since influx European colonists. Over preceding 10 millennia, areas already settled proactively managed with intentional burning by tribes. Prichard then on management historically applied tribes currently some intentionally manage forests for resilient conditions. They address questions surrounding application relevance these practices. Here, we highlight main findings both papers offer recommendations management. We discuss progress paralysis often occurs strict adherence precautionary principle; insights dealing common problem irreducible uncertainty suggestions reframing policy direction; key knowledge gaps needs.

Language: Английский

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Ancient grasslands guide ambitious goals in grassland restoration

Science, Journal Year: 2022, Volume and Issue: 377(6606), P. 594 - 598

Published: Aug. 4, 2022

Grasslands, which constitute almost 40% of the terrestrial biosphere, provide habitat for a great diversity animals and plants contribute to livelihoods more than 1 billion people worldwide. Whereas destruction degradation grasslands can occur rapidly, recent work indicates that complete recovery biodiversity essential functions occurs slowly or not at all. Grassland restoration-interventions speed guide this recovery-has received less attention restoration forested ecosystems, often due prevailing assumption are recently formed habitats reassemble quickly. Viewing grassland as long-term assembly toward old-growth endpoints, with appreciation feedbacks threshold shifts, will be crucial recognizing when how globally important ecosystem.

Language: Английский

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Measuring the success of climate change adaptation and mitigation in terrestrial ecosystems

Science, Journal Year: 2019, Volume and Issue: 366(6471)

Published: Dec. 13, 2019

Measuring mitigation and adaptation As more carbon dioxide is emitted into the atmosphere, humans natural world are beset by damaging consequences of a rapidly changing climate. Natural seminatural ecosystems likely to be best starting place for immediate solutions. First, though, many environments need restoration maximize their own resilience climate change. In reviewing our options, Morecroft et al. point out that we can directly observe success strategies quantifying atmospheric dioxide. Successful challenging because it involves range social biodiversity measures. However, could make matters worse if do not constantly monitor effects interventions devise react flexibly as conditions unfold. Science , this issue p. eaaw9256

Language: Английский

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Hysteresis of tropical forests in the 21st century

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Oct. 5, 2020

Abstract Tropical forests modify the conditions they depend on through feedbacks at different spatial scales. These shape hysteresis (history-dependence) of tropical forests, thus controlling their resilience to deforestation and response climate change. Here, we determine emergent from local-scale tipping points regional-scale forest-rainfall across tropics under recent a severe climate-change scenario. By integrating remote sensing, global hydrological model, detailed atmospheric moisture tracking simulations, find that feedback expands geographic range possible forest distributions, especially in Amazon. The Amazon could partially recover complete deforestation, but may lose later this century. Congo currently lacks resilience, is predicted gain it change, whereas Australasia are resilient both current future climates. Our results show how own distributions create climatic enable them.

Language: Английский

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The global potential for increased storage of carbon on land

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(23)

Published: May 31, 2022

Significance Despite increased interest in land-based carbon storage as a climate solution, there are physical limits on how much additional can be incorporated into terrestrial ecosystems. To effectively determine where and to act, jurisdictions need robust data illustrating the magnitude distribution of opportunities increase storage, well information actions available achieve that storage. Here, we provide globally consistent maps for directing under current future climate, framework determining could gained through restoration, improved management, or maintenance woody biomass soil organic matter. Our estimates an upper bound land stewardship mitigate crisis.

Language: Английский

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Biodiversity–productivity relationships are key to nature-based climate solutions

Nature Climate Change, Journal Year: 2021, Volume and Issue: 11(6), P. 543 - 550

Published: June 1, 2021

Language: Английский

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