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Commit bb5a6caa authored by Lisa Wiesner's avatar Lisa Wiesner
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Update file hptimelinedata.tsx

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......@@ -1521,20 +1521,18 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
Winkeljann has a wealth of experience in the field of RNA therapeutics and nanotechnology. His background includes extensive research in the
development of lipid-based delivery systems, focusing on optimizing stability and efficacy for therapeutic applications. Winkeljann’s work
is supported by cutting-edge research from academic institutions, including collaborations with Professor Olivia Merkel from the
Ludwig-Maximilians-Universität in Munich, Germany, since his doctoral thesis in her working group. The interview with Winkeljann promoted
Ludwig-Maximilians-Universität in Munich, Germany. The interview with Winkeljann promoted
our project part, which aimed to utilize spray-dried LNPs for efficient delivery to the lung. By engaging with RNhale, we
sought to understand the nuances of their nano-embedded microparticle technology and how it could enhance our delivery systems. </p>],
insights: [<p>RNhale's technology leverages advanced spray drying techniques to stabilize and deliver RNA therapeutics. During our interview,
sought to understand the nuances of their nano-embedded microparticle (NEM) technology and how it could enhance our delivery systems. </p>],
insights: [<p>RNhale's technology leverages advanced spray drying techniques to stabilize RNA therapeutics and create a formulation for pulmonary delivery. During our interview,
Winkeljann detailed several crucial aspects. Firstly, the stability and shelf-life of spray-dried LNPs are remarkable. RNhale’s siRNA
formulations have maintained their integrity for up to 18 months at room temperature, and although specific data for mRNA is still pending,
this suggests a promising shelf-life for mRNA formulations under similar conditions. The spray drying process itself involves mixing an ethanol
phase containing lipids with an aqueous phase containing RNA. This mixture is then spray-dried, forming LNPs as tiny spherical particles.
Key parameters for this process include maintaining an internal drying temperature of around 100 °C and using excipients like lactose to
preserve the nanoparticles' structure and function​ <TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />. </p>,
<p>Ensuring the integrity and efficiency of the LNPs involves various methods, including gel electrophoresis, blotting, and functional readouts through transfection assays.
After drying, the nanoparticles retain their spherical structure, which resembles that of "golf balls" under scanning electron microscopy (SEM)<TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />.
this suggests a promising shelf-life for mRNA formulations under similar conditions. The manufacturing process itself involves formulating RNA loaded LNPs through rapid mixing. Subsequently the LNPs are blended with a stabilizing excipient, often a sugar or alcohol. This mixture is then spray-dried, forming so-called NEMs, micron-sized particals compirsing an excipient matrix that embeds the RNA carrying LNPs.
Key parameters for this process include LNP composition, feed rate, RNA content and drying temparture ​ <TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />. </p>,
<p>Verifying the integrity and efficiency of the LNPs involves various methods, including gel electrophoresis, scattering techniques, and functional readouts through transfection assays.
After drying, the NEMs exhibit sperical shape, with sizes between 1-5µm which can be visualized by scanning electron microscopy (SEM)<TabScrollLink tab="rnhale" scrollId="desc-1" num="1" />.
Moreover, RNhale employs artificial intelligence to optimize LNP formulations and predict the best drying conditions, reducing the need for
extensive wet lab work. This AI-driven approach enhances efficiency and reliability in developing therapeutic nanoparticles. </p>],
extensive wet lab work.</p>],
implementation: [
<p>The interview with Dr. Benjamin Winkeljann from RNhale provided invaluable insights that will significantly enhance our project
focused on mRNA delivery to the lungs using spray-dried LNPs. By seeking to integrate their proven techniques and innovative approach
......@@ -1545,19 +1543,18 @@ export const timelinedata: Array<TimelineDatenpunkt> = [
pictureurl_implementation: "https://static.igem.wiki/teams/5247/photos/for-wiki-texts/del-interview-rnhale/paper-sem.jpg",
references: <RnhaleSources />,
/* interview:<>
<QaBox q="Can you specify the shelf life for spray-dried LNPs? What storage conditions do you recommend to maximize stability?" a="For small interfering RNA, we can guarantee a shelf life of 18 months at room temperature. However, there are no existing studies for mRNA, which tends to be more fragile. For optimal stability, we recommend storing LNPs in a cool, dry place, away from direct sunlight."/>
<QaBox q="What technical requirements and equipment are necessary to successfully spray-dry LNPs using your nano-embedded-microparticle (NEM) technology?" a="The spray-drying process for LNPs using our NEM technology involves several technical steps. Initially, a mixture of an ethanol phase containing lipids and another phase with RNA is prepared. This mixture is then subjected to a spray-drying process where droplets are sprayed into a drying tower. The liquid evaporates, leaving behind LNPs as small spherical particles."/>
<QaBox q="How complicated is the protocol for producing spray-dried LNPs? Can you describe the protocol?" a="The protocol, while detailed, is straightforward. It involves preparing the lipid and RNA mixture, followed by the spray-drying process where droplets are sprayed into a drying tower. As the liquid evaporates, the LNPs remain as small beads. This process is critical for ensuring the correct size and composition of the LNPs."/>
<QaBox q="How do LNPs appear after the drying process?" a="After drying, LNPs resemble golf balls on a micron scale when observed under a scanning electron microscope (SEM). Their size distribution is analyzed through light scattering measurements, among other techniques."/>
<QaBox q="How do you ensure that the RNA cargo remains stable despite the heat during the drying process?" a="We mitigate the impact of heat by optimizing the drying conditions. Chitosan and PEG can also influence stability. Without PEG, LNPs may agglomerate and become non-functional, but too much PEG can render them inert. Therefore, a balanced approach is necessary, though PEG has no significant impact on the drying process itself."/>
<QaBox q="At what temperature is the LNP dried?" a="The internal temperature during the drying process is approximately 100 degrees Celsius, as noted in our publications."/>
<QaBox q="Can you specify the shelf life for spray-dried LNPs? What storage conditions do you recommend to maximize stability?" a="For small interfering RNA, we ofhave demonstrated and published stability of 18 months at room temperature. However, there are no existing studies for mRNA, which tends to be more fragile. For optimal stability, we recommend storing dried LNPs in a cool, dry place, away from direct sunlight."/>
<QaBox q="What technical requirements and equipment are necessary to successfully spray-dry LNPs using your nano-embedded-microparticle (NEM) technology?" a="The key equipment includes an Impingement Jet Mixer for the preparation of LNPs and a spray dryer for formulating the dry powder. In combination with standard laboratory equipment such as mixers, pipettes, etc., this setup is sufficient to produce NEMs as described in our publications. However, to monitor the process and assess the quality of both intermediate and final products, a variety of analytical methods is required, including Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Plate Reader, cell culture equipment, and a laser diffractometer. This setup makes it quite costly to establish the entire process."/>
<QaBox q="How complicated is the protocol for producing spray-dried LNPs? Can you describe the protocol?" a="The spray-drying process for LNPs using our NEM technology involves several technical steps. Initially, a mixture of an ethanol phase containing lipids and another phase with RNA is prepared. This mixture is then subjected to an Impingement Jet Mixer to formulate RNA-loaded LNPs. Subsequently the LNPs are mixed with a stabilizing excipient. This mixture is fed into a spray-drier where the solution is aerosolized into a heated drying tower. The liquid evaporates, leaving behind NEMs as small spherical particles, which can then be loaded into capsules for use with a dry powder inhaler (DPI)."/>
<QaBox q="How do LNPs appear after the drying process?" a="In the dry state, LNPs cannot be visualized, as they are embedded within the NEM structure. However, we assess the LNP structure and morphology after redispersion of the NEMs, a process that also occurs upon inhalation and contact with lung fluids. While we observe a slight increase in LNP size after redispersion, the particles remain intact, retaining their spherical shape and RNA loading, as demonstrated by various techniques, including cryo-TEM imaging."/>
<QaBox q="How do you ensure that the RNA cargo remains stable despite the heat during the drying process?" a="We mitigate the impact of heat by optimizing the drying conditions such as temperature, feed rate and time of heat exposure. Different components in the excipient mix, or the LNPs, such as the PEGylated lipid can also influence stability during and post drying. Without PEG or with too little PEG-lipid, LNPs may agglomerate and become non-functional, but too much PEG can render them inert and thus limit cellular uptake."/>
<QaBox q="At what temperature is the LNP dried?" a="The inlet temperature during the spraydrying process is approximately 120 degrees Celsius, as noted in our publications."/>
<QaBox q="Does each LNP formulation require individual testing?" a="Yes, each LNP with a unique composition needs to be tested individually to ensure optimal stability and performance."/>
<QaBox q="How can we test the efficiency of LNPs after the drying process?" a="The efficiency can be tested through transfection studies. Additionally, the particles can be broken down to analyze the mRNA structure, although this is a more complex and time-consuming process."/>
<QaBox q="Can you elaborate on how you use AI to customize LNPs? What exactly does the AI do, and how reliable is it?" a="Our AI is used for screening, optimization, and the design of experiments, significantly reducing wet lab work. It also plays a role in developing new lipids, a process more closely associated with the work of Olivia Merkel."/>
<QaBox q="What properties of LNPs could hinder the drying process?" a="Theoretically, nothing should hinder the drying process if it is optimized for the specific cargo and target. Adjustments can always be made to accommodate different formulations."/>
<QaBox q="In your opinion, which LNPs are best suited for the drying process (SLNs, NLCs, etc.)?" a="It depends on the specific application and composition of the LNPs."/>
<QaBox q="What are the estimated costs for the entire drying process?" a="The primary expenses are in raw materials and formulations, which are relatively expensive. The process itself can cost in the four-digit range."/>
<QaBox q="Would you be willing to support us in our project? Would you dry our LNPs?" a="The spray dryer requires 5 mL of a solution with 5% lipid solids and 0.02% RNA. We’ve published recovery rates of 70%. You can send us the mRNA and LNP components to encapsulate and dry."/>
<QaBox q="What are the estimated costs for the entire drying process?" a="The primary expenses are in raw materials and for the formulationspecifically RNA and lipids, which are relatively expensive. Other consumables, such as process fluids, are comparatively inexpensive. The manufacturing process itself is cost-effective; however, overall expenses will vary based on production volume and equipment utilization rates."/>
<QaBox q="Would you be willing to support us in our project? Would you dry our LNPs?" a="The spray dryer requires 5 mL of a solution with 5% solid content. Among these solids, the lipid content can be adjusted between approximately 0.2% and 15%, while the RNA content can range from 0.02% to 1.5%. The remaining percentage is composed of excipients. We’ve published recovery rates of >70%. You can send us the mRNA and LNP components to encapsulate and dry."/>
</>, */
summary: "The conversation focused on spray-drying LNPs, emphasizing the shelf life of RNA-based formulations, optimal storage conditions, and technical requirements for the drying process. Corden Pharma shared insights on the protocol, highlighting the need for testing each LNP formulation individually for stability. AI technology is used to optimize LNP formulations, and potential collaborations were discussed, including support for drying LNPs.",
months: "august"
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