Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications.

Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique asymmetric tails and two dissimilar degradable moieties incorporated within the structure. Lipids tails of varying lengths, degrees of unsaturation, branching, and the inclusion of additional ester moieties were evaluated for protein expression. We observed several key lipid structure activity relationships that correlated with improved protein production in vivo, including lipid tails of 12 carbons on the ester side and the effect of carbon spacing on the disulfide arm of the lipids. Differences in LNP physical characteristics were observed for lipids containing an extra ester moiety. The LNP structure and lipid bilayer packing, visualized through Cryo-TEM, affected the amount of protein produced in vivo. In non-human primates, the Good HEPES LNPs formulated with an mRNA encoding an influenza hemagglutinin (HA) antigen successfully generated functional HA inhibition (HAI) antibody titers comparable to the industry standards MC3 and SM-102 LNPs, demonstrating their promise as a potential vaccine.

A critical analysis of ecosystem services as a tool in conservation projects: the possible perils, the promises,and the partnerships.

Human modifications of the environment are growing in number and geographic extent, expanding to all of the Earth's surfaces and affecting the vast majority of the Earth's natural resources. Increases in demand for resources, growing levels of poverty, and more extensive urbanization, among other changes, lead to a need to move beyond parks and classic conservation approaches to incorporate humans and working landscapes more directly in conservation efforts. One approach to do this is to focus on ecosystem services, the benefits ecosystems provide to humans. Here conservation projects that focus only on biodiversity are analytically compared with those that include ecosystem-service goals to dispel myths and explore promises. Projects conducted by The Nature Conservancy, the world's largest conservation organization, are used, and it is demonstrated that not only do ecosystem-service approaches engage new landscapes, stakeholders, and funding sources, but that they do so without neglecting traditional biodiversity goals and the traditional approaches of protection and preservation. Seven case studies that uniquely create a broker-type structure to determine how to distribute money for the provision of particular services to the satisfaction of a wide range of stakeholder interests are focused on. It is found that all use local, independent leadership to initiate partnership formation, which then leads to the creation of a separate institutional entity that has legal rights to determine fund provision. The activities encouraged by these entities, and which therefore appear to satisfy a wide array of interests, are supporting education, rewarding best management practice, creating jobs, and monitoring outcomes.

Field evidence that ecosystem service projects support biodiversity and diversify options.

Ecosystem service approaches to conservation are being championed as a new strategy for conservation, under the hypothesis that they will broaden and deepen support for biodiversity protection. Where traditional approaches focus on setting aside land by purchasing property rights, ecosystem service approaches aim to engage a much wider range of places, people, policies, and financial resources in conservation. This is particularly important given projected intensification of human impacts, with rapid growth in population size and individual aspirations. Here we use field research on 34 ecosystem service (ES) projects and 26 traditional biodiversity (BD) projects from the Western Hemisphere to test whether ecosystem service approaches show signs of realizing their putative potential. We find that the ES projects attract on average more than four times as much funding through greater corporate sponsorship and use of a wider variety of finance tools than BD projects. ES projects are also more likely to encompass working landscapes and the people in them. We also show that, despite previous concern, ES projects not only expand opportunities for conservation, but they are no less likely than BD projects to include or create protected areas. Moreover, they do not draw down limited financial resources for conservation but rather engage a more diverse set of funders. We also found, however, that monitoring of conservation outcomes in both cases is so infrequent that it is impossible to assess the effectiveness of either ES or BD approaches.