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Awaiting IPO, Poseida Therapeutics nips in a quick $110M series D

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Last week, CAR-T biotech Poseida Therapeutics said it was gunning for another IPO attempt a year after ditching it in favor of a new funding round led by Novartis.

This time, the IPO is still going ahead, but, in the middle of it, the company has announced a new $110 million funding round ahead of its $115 million public offering attempt.

Novartis didn’t appear on its statement this time, with the financing led by funds advised by Fidelity Management Research Company with help from Adage Capital Management and Schonfeld Strategic Advisors. “A number of current investors also participated in the financing,” the biotech added in its brief update.

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How the fast-changing R&D pipeline is amplifying the importance of adaptable CROs

The story of CMIC’s rise from being a startup in a one-room apartment to a multinational leader is defined by an ability and readiness to foresee the changing needs of biopharma companies and adapt accordingly. With pipelines primed to continue evolving in the coming years, that adaptable approach is now more important than ever.

In April last year, the cell therapy player put the kibosh on original its IPO plans, settling instead for a $142 million series C round with more than half of the money coming from cell and gene therapy devotee Novartis.

The Big Pharma put up a $75 million equity investment in the San Diego-based company, which has a stable of CAR-T candidates manufactured through a nonviral process.

The expected IPO cash and its series D is earmarked for Poseida’s leading candidate P-BCMA-101, an autologous CAR-T currently in a potentially registrational phase 2 trial for multiple myeloma.

“This financing supports the approach we are taking to leverage our broad proprietary gene engineering platform technologies, including the piggyBac DNA Modification System and Cas-CLOVER site-specific gene editing system, for the creation of numerous differentiated cell and gene therapy product candidates,” said Eric Ostertag, M.D., Ph.D., CEO at Poseida.

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Source: https://www.fiercebiotech.com/biotech/awaiting-ipo-poseida-therapeutics-nips-a-quick-110m-series-d

Biotechnology

Getting a grasp on India’s malaria burden

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A method that involves infecting liver cells with mosquito-bred parasites could improve the study of malaria in India

A new approach could illuminate a critical stage in the life cycle of one of the most common malaria parasites. The approach was developed by scientists at Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS) in Japan and published in the Malaria Journal.

“The Plasmodium vivax malaria parasite can stay dormant in a person’s liver cells up to years following infection, leading to clinical relapses once the parasite is reactivated,” says Kouichi Hasegawa, an iCeMS stem cell biologist and one of the study’s corresponding authors.

P. vivax is responsible for around 7.5 million malaria cases worldwide, about half of which are in India. Currently, there is only one licensed drug to treat the liver stage of the parasite’s life cycle, but it has many side effects and cannot be used in pregnant women and infants. The liver stage is also difficult to study in the lab. For example, scientists have struggled to recreate high infection rates in cultured liver cells.

Hasegawa and his colleagues in Japan, India and Switzerland developed a successful system for breeding mature malaria parasites, culturing human liver cells, and infecting the cells with P. vivax. While it doesn’t solve the high infection rate problem, the system is providing new, localized insight into the parasite’s liver stage.

“Our study provides a proof-of-concept for detecting P. vivax infection in liver cells and provides the first characterization of this infectious stage that we know of in an endemic region in India, home to the highest burden of vivax malaria worldwide,” says Hasegawa.

The researchers bred Anopheles stephensi mosquitos in an insectarium in India. Female mosquitos were fed with blood specifically from Indian patients with P. vivax infection.

Two weeks later, mature sporozoites, the infective stage of the malaria parasite, were extracted from the mosquitos’ salivary glands and added to liver cells cultured in a petri dish.

The scientists tested different types of cultured liver cells to try to find cells that would be infected by lots of parasites like in the human body. Researchers have already tried using cells taken liver biopsies and of various liver cancer cell lines. So far, none have led to large infections.

Hasegawa and his colleagues tried using three types of stem cells that were turned into liver cells in the lab. Notably, they took blood cells from malaria-infected patients, coaxed them into pluripotent stem cells, and then guided those to become liver cells. The researchers wondered if these cells would be genetically more susceptible to malaria infection. However, the cells were only mildly infected when exposed to the parasite sporozoites.

A low infection rate means the liver cells cannot be used for testing many different anti-malaria compounds at once. But the researchers found the cells could test if a specific anti-malaria compound would work for a specific patient’s infection. This could improve individualized treatment for patients.

The scientists were also able to study one of the many aspects of parasite liver infection. They observed the malaria protein UIS4 interacting with the human protein LC3, which protected the parasite from destruction. This demonstrates their approach can be used to further investigate this important stage in the P. vivax life cycle.

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DOI: 10.1186/s12936-020-03284-8

About Kyoto University’s Institute for Integrated Cell-Material Sciences (iCeMS):

At iCeMS, our mission is to explore the secrets of life by creating compounds to control cells, and further down the road to create life-inspired materials.
https://www.icems.kyoto-u.ac.jp/

For more information, contact:

I. Mindy Takamiya/Mari Toyama

[email protected]

Source: https://bioengineer.org/getting-a-grasp-on-indias-malaria-burden/

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Biotechnology

More ecosystem engineers create stability, preventing extinctions

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When we think of engineering in nature, we tend to think of beavers — the tree-felling, dam-building rodents whose machinations can shape the landscape by creating lakes and changing the path of rivers. But beavers are far from the only organisms to reshape their environment. A squirrel who inadvertently plants oak trees is also an “ecosystem engineer” — roughly speaking, any organism whose impact on the environment outlasts its own lifetime. The coolest of these biological builders, according to Justin Yeakel, might be the shipworm, which eats through rocks in streams, creating cozy abodes for future invertebrate inhabitants.

Yeakel, an ecologist at the University of California, Merced, and a former Santa Fe Institute Omidyar Fellow is the lead author of a new paper that models the long term impact of ecosystem engineers. Researchers have long considered the role of ecosystem engineers in natural histories, but this study is among the first to quantitatively assess them in an ecological network model.

“We wanted to understand how food webs and interaction networks were established from a mechanistic perspective,” he says. “To do that, you have to include things like engineering because species influence their environment and there’s this feedback between the environment to the species.”

In particular, the model uses simple rules to show how food webs can be assembled, how species interactions can change over time, and when species go extinct. One striking result: Few ecosystem engineers led to many extinctions and instability while many ecosystem engineers led to stability and few extinctions.

“As you increase the number of engineers, that also increases the redundancy of the engineers and this tends to stabilize the system,” Yeakel says.

So, how do you create an ecological network model? It’s highly abstracted — there are no specific species like beavers or concrete environmental features like rivers. Everything is reduced to interactions: species can eat, need, or make. In this sense, nature becomes a network of interactions. For example, bees eat nectar from flowers; flowers need bees to be pollinated; trees make shade which flowers need.

The researchers gave the model a small number of rules, the main one being: Species have to eat only one thing to survive but they have to obtain all of the things they need. In less abstract terms, even if one flower species goes extinct, bees could survive on nectar from other flowers. But if either bees or trees fail to provide pollination or shade, which flowers need, then the flowers will go extinct.

Using these rules, the models were able to produce ecological networks similar to those in the real world, with a characteristic hourglass shape in species diversity — more diversity at the top and the bottom of the web, less in the middle. To expand the model for future research, Yeakel plans on incorporating evolutionary dynamics so that species can change what they eat and need and make.

Two and a half billion years before humans showed up, cyanobacteria were a planetary-scale engineer that slowly changed the composition of the entire atmosphere by oxygenating it. But unlike our photosynthetic predecessors, “we’re making changes on ecological timescales rather than evolutionary timescales,” Yeakel says. “Is an organism that becomes a planetary-scale engineer doomed to extinction if it changes the environment too quickly?”

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Source: https://bioengineer.org/more-ecosystem-engineers-create-stability-preventing-extinctions/

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Lab-Grown ‘Mini-Brains’ Suggest COVID-19 Virus Can Infect Brain

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How coronavirus infects brain cells?
–Sharing is Caring–

   Mini-brain study: How coronavirus can infect human brain cells?

A study revealed that the SARS-CoV-2 can infect the organoids – tiny tissue cultures made from human cells that replicate entire body organs known as “mini-brains”. The study was carried out by a team from two Johns Hopkins University institutions, consisting of infectious disease specialists from the school of medicine, and neurotoxicologists and virologists from the Bloomberg School of Public Health.

The outcomes of the study titled “Infectability of human BrainSphere neurons suggest neurotropism of SARS-CoV-2” were posted in the journal ALTEX: Alternatives to Animal Experimentation.

According to the early reports from Wuhan, 36% of patients with the COVID-19 show neurological signs and symptoms, however, whether or not the coronavirus infects human brain cells is not clear yet. The research showed the ACE2 receptor that the SARS-CoV-2 virus uses to enter the lungs is also present in the human neurons. So, they theorized, ACE2 may also offer access to the brain.

The study found – evidence of infection and replication of the pathogen when SARS-CoV-2 virus particles were introduced into a human mini-brain model – what is thought to be the first time.

Naturally, the blood-brain barrier protects the human brain from numerous viruses, bacteria, and chemical agents, it often protects against brain infections. Thomas Hartung, M.D., Ph.D., chair for evidence-based toxicology, the Bloomberg School of Public Health said, whether the SARS-CoV-2 virus passes this barrier or not is yet to be shown. But, it is understood that the blood barrier disintegrates during severe inflammations, such as those observed in COVID-19 individuals.

He added the impermeability of the blood-brain barrier can also offer a problem for drug designers targeting the brain.

The impact of SARS-CoV-2 on the developing brain is an additional issue elevated by the research. Prior research from Paris-Saclay University has shown that the virus crosses the placenta, and most notably during the early development, the embryos lack the blood-brain barrier – this can increase the risk of brain infections. Hartung said we have no proof that the developmental disorders can be caused by the viruses.

But, the ACE2 receptor is present in the “mini-brains” from their earliest stages of development. Hartung claims that the outcomes of the study suggest that during pregnancy extra care needs to be taken.

William Bishai, M.D., Ph.D., professor of medicine, the Johns Hopkins University School of Medicine, and leader of the infectious disease team for the study said this study is an additional crucial step in our understanding of how infection results to symptoms, and where we might treat COVID-19 with drugs.

The mini-brain models known as BrainSpheres were derived from human stem cells and developed at the Bloomberg School of Public Health 4 years ago. These BrainSpheres were the first mass-produced, highly standardized organoids of their kind, and have actually been utilized to model a number of diseases, consisting of infections by viruses such as HIV, dengue, and Zika.

Source

Author: Sruthi S

Source: https://www.biotecnika.org/2020/07/how-coronavirus-infects-brain-cells-mini-brain-study-reveals-the-secret/

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