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cover of episode Targeted mRNA therapy tackles deadly pregnancy condition in mice

Targeted mRNA therapy tackles deadly pregnancy condition in mice

2024/12/11
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Nature Podcast

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D
Dan Fox
D
Davide Castelvecchi
K
Kelsey Swingle
M
Mike Mitchell
N
Nick Kalagropoulos
Topics
Emily Bates和Nick Pettichow:研究人员开发了一种利用mRNA治疗妊娠期高血压疾病的方法,这种疾病会导致孕妇和胎儿的死亡。 Kelsey Swingle:目前临床上治疗妊娠期高血压疾病的方法只能缓解症状,无法解决根本问题,很多时候需要提前引产。 Mike Mitchell:研究团队发现脂质纳米颗粒(LNP)递送的mRNA能够到达胎盘,这为治疗妊娠期高血压疾病提供了新的思路。 Kelsey Swingle:研究团队利用VEGF mRNA来促进胎盘血管生成,改善血液流动,从而治疗妊娠期高血压疾病。通过高通量筛选找到了能够高效递送mRNA到胎盘的脂质纳米颗粒。在小鼠模型中,该疗法能够有效降低血压,并改善胎儿发育,效果显著。小鼠和人类的胎盘存在差异,该疗法需要进一步优化才能应用于人类。 Mike Mitchell:该疗法能够显著改善妊娠期高血压疾病小鼠模型中胎儿的生长发育,该疗法中脂质纳米颗粒的化学性质决定了其与哪些蛋白质相互作用,从而影响其在体内的分布。

Deep Dive

Key Insights

What is preeclampsia and why is it a significant issue in pregnancy?

Preeclampsia is a pregnancy complication characterized by high blood pressure and reduced blood flow in the placenta, causing 15% of maternal deaths and 25% of fetal deaths worldwide. Current treatments only manage symptoms, not the underlying causes.

How does the mRNA therapy work in treating preeclampsia in mice?

The therapy involves delivering mRNA for a blood-vessel growth factor (VEGF) into the placenta using lipid nanoparticles, stimulating the production of extra blood vessels and reducing high blood pressure associated with preeclampsia.

Why did the researchers choose to use lipid nanoparticles for mRNA delivery?

Lipid nanoparticles were chosen because they can accumulate in the placenta, delivering mRNA to cells like trophoblasts and endothelial cells, which are crucial for blood vessel formation and function.

What challenges did the researchers face in targeting the placenta specifically?

Most lipid nanoparticles (LNPs) tend to accumulate in the liver, so the team had to screen a library of 100 LNPs to find one that delivered mRNA more effectively to the placenta than to the liver.

What were the results of the mRNA therapy in mouse models of preeclampsia?

The therapy reduced hypertension almost instantaneously and maintained lower blood pressure through the end of gestation, leading to healthier fetuses with improved nutrient and oxygen transport.

What are the next steps for translating this therapy to human use?

Future research will involve testing in animals with placentas closer to humans, such as guinea pigs, and determining the optimal dosing regimen for longer human pregnancies.

What are G-protein-coupled receptors (GPCRs) and why are they significant in cell behavior?

GPCRs are a large family of cell surface receptors that control various cellular processes, including sensing light, fighting pathogens, and secreting hormones. They are crucial for cells to respond appropriately to their environment.

How did the researchers modify GPCRs to control cell behavior?

The team added a molecular component that blocked GPCR activity but could be removed in response to specific signals, allowing them to activate these receptors on command and control cell behavior.

What are the potential applications of this GPCR modification platform?

The platform can control a wide range of cell behaviors, including gene expression, secretion of molecules like cytokines, and even neuronal activity, opening up possibilities for new therapeutics.

What is the significance of Google's milestone in quantum computing?

Google's achievement shows that quantum computers can become more accurate as they scale up, a goal researchers have been striving for decades. This could bring quantum computing closer to practical applications.

How does error correction work in quantum computing?

Error correction in quantum computing involves spreading the quantum information across multiple qubits in a redundant way, allowing detection and correction of errors without spoiling the quantum state.

What was unique about Google's approach to improving quantum error correction?

Google improved the quality of all components in their quantum computer, ensuring that each step contributed to reducing errors. This systematic improvement allowed error correction to work effectively as the system scaled up.

Chapters
Researchers are developing an mRNA-based therapy to treat pre-eclampsia, a deadly pregnancy complication. The therapy involves delivering mRNA to the placenta to stimulate the production of blood vessels, thereby reducing high blood pressure. Early tests in mice have shown promising results, with the potential to reduce hypertension and improve fetal health.
  • mRNA-based therapy reverses pre-eclampsia causes in mice
  • Delivers mRNA to mouse placentas to stimulate blood vessel growth
  • Reduces high blood pressure associated with pre-eclampsia
  • Promising results in mice, but human trials are needed

Shownotes Transcript

00:45 A potential treatment for pre-eclampsia

Researchers have shown in mice experiments that an mRNA-based therapy can reverse the underlying causes of pre-eclampsia, a deadly complication of pregnancy for which treatment options are limited. Inspired by the success of mRNA vaccines, the team behind the work designed a method to deliver the genomic instructions for a blood-vessel growth factor directly into mouse placentas. This stimulated the production of extra blood vessels reducing the very high-blood pressure associated with the condition. Pre-eclampsia causes 15% of maternal deaths and 25% of foetal and newborn deaths worldwide and although the work is early and human trials will be required, the team hope that this work demonstrates the potential of using this approach to treat pre-eclampsia.

*Research Article: *Swingle et al.)

11:00 Research Highlights

Stacks of, mass-produced bowls suggest that people founded, but then abandoned an ancient Mesopotamian civilization, and analysis of Venus’s gases suggests that the planet was always dry.

*Research Highlight: *Ancient stacks of dishes tell tale of society’s dissolution)

*Research Highlight: *Has Venus ever had an ocean? Its volcanoes hint at an answer)

13:29 Programmable cellular switches

A team of scientists have created cellular switches on the surface of cells, allowing them to control their behaviour. Creating these switches has been a long-term goal for synthetic biologists — especially a group of proteins called G-protein-coupled receptors that already control many cellular processes. However, engineering these proteins has been challenging, as modifications can ruin their function. Instead, the team added another molecular component that blocked the receptors activity, but could be removed in response to specific signals. This allowed the researchers to activate these receptors on command, potentially opening up a myriad of new ways to control cell behaviour, such as controlling when neurons fire.

*Research Article: *Kalogriopoulos et al.)

19:35 Google reaches a milestone in quantum computing

A team at Google has shown it is possible to create a quantum computer that becomes more accurate as it scales up, a goal researchers have been trying to achieve for decades. Quantum computing could potentially open up applications beyond the capabilities of classical computers, but these systems are error-prone, making it difficult to scale them up without introducing errors into calculations. The team showed that by increasing the quality of all the components in a quantum computer they could create a system with fewer errors, and that this trend of improvement continued as the system became larger. This breakthrough could mean that quantum computers are getting very close to realising the useful applications that their proponents have long promised.

Nature:* ‘A truly remarkable breakthrough’: Google’s new quantum chip achieves accuracy milestone*)

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