diff --git a/src/contents/description.tsx b/src/contents/description.tsx
index 8541cdcb2568be510e42375c0ce9a2dfa3b30616..a0324f105a1fa775590e770ee95b16fad74e675b 100644
--- a/src/contents/description.tsx
+++ b/src/contents/description.tsx
@@ -189,7 +189,34 @@ export function Description() {
</div>
</div>
<Collapsible id="Col1" open={false} title="LNPs explained">
- <LoremShort/>
+ <H4 text="LNPs and their impact on modern medicine" id="text" />
+ <p>Lipid nanoparticles (LNPs) are an advanced delivery system designed to transport therapeutic molecules like RNA, DNA or proteins into the cells. These nanoparticles are tiny spheres made of lipids that form a protective shell around the cargo. The size of LNs typically ranges from 50 to 200 nm in diameter, making them incredibly small - about 1,000 times thinner than a human hair [1]. </p>
+ <p>Overall, LNPs represent a significant advancement in drug delivery technology. LNPs offer exceptionally high drug-loading capacities, making them highly effective for delivering substantial amounts of therapeutic agents in a single dose. Their advanced design allows for the encapsulation of a large payload, which enhances the efficacy of treatments and reduces the frequency of administration [3]. By encapsulating and protecting therapeutic agents like mRNA, LNPs enhance the stability, targeted delivery, and effectiveness of treatments. Their ability to be tailored for specific delivery needs, such as targeting particular organs or overcoming physiological barriers, makes them a powerful tool in modern medicine [9].</p>
+ <H4 text="Protection of cargo" id="text" />
+ <p> The primary function of LNPs is to shield the therapeutic agents they carry, such as mRNA, from degradation and facilitate their delivery into cells. mRNA is a critical component in many modern vaccines and therapies, but it is highly susceptible to breaking down before it can reach its target within cells. LNPs address this challenge by encapsulating the mRNA, thus protecting it from harmful enzymes, like RNases and environmental conditions [2]. </p>
+ <H4 text="Delivery assurance" id="text" />
+ <p>LNPs come in various types tailored for different therapeutic needs. Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) enhance drug stability and solubility, while Liposomes, with their bilayer structure, are versatile for encapsulating both hydrophilic and hydrophobic drugs. Cationic LNPs are ideal for gene delivery due to their positive charge, whereas anionic and neutral LNPs offer reduced interaction and lower toxicity, respectively [3]. </p>
+ <p>To enhance their effectiveness, LNPs are designed with specific components. For instance, the Nebulized Lung Delivery 1 (NLD1) nanoparticle, a particular type of LNP, includes a combination of lipids and polymers that stabilize the mRNA and allow it to be delivered efficiently. This formulation includes small lipid particles that encapsulate the mRNA and can maintain stability for several days under proper storage conditions [2]. </p>
+ <H4 text="Size impact of pulmonary LNPs" id="text" />
+ In the context of pulmonary delivery, where the goal is to target the lungs, the size and properties of the LNPs are crucial. Particles smaller than 2 micrometers are particularly effective for reaching the alveolar regions of the lungs [11].
+ <H4 text="Role of surface modifications in targeting" id="text" />
+ <p>LNPs are pivotal not only for shielding mRNA but also for ensuring its efficient delivery into target cells. They facilitate cellular uptake through endocytosis, where the cell membrane engulfs the nanoparticle. LNPs are acclaimed for their high drug-loading capacities, which greatly enhance their therapeutic effectiveness. However, the success of this delivery hinges on effective endosomal escape. Ideally, LNPs release their mRNA payload into the cytoplasm after escaping from endosomes. If this escape process is inefficient, the mRNA can be degraded by lysosomes, which poses a significant challenge for mRNA vaccines and therapies [4].</p>
+ <p>A crucial advancement in LNP technology involves the use of pH-sensitive cationizable lipids. These lipids remain neutral at physiological pH but become cationic in the acidic environment of endosomes. This shift in charge helps dissociate the nanoparticles and disrupt the endosomal membrane, enhancing the likelihood of successful endosomal escape [5]. </p>
+ <p>Moreover, the surface of LNPs can be customized to improve targeting. For instance, incorporating specific lipids or modifying the surface with charged groups can direct the delivery of mRNA to targeted organs like the lungs or spleen [6]. Additionally, LNPs can be engineered with targeting ligands or antibodies to precisely direct their payload to specific cell types, further enhancing their therapeutic efficacy [7]. Another approach can be chitosan-based nanoparticles have been explored for their ability to adhere to mucus and enhance drug delivery through the respiratory tract. These nanoparticles can penetrate through the mucus layer to reach the lung tissues more effectively [8]. This versatility in design is essential for optimizing the delivery and effectiveness of LNP-based therapies.</p>
+ <div className='row align-items-center'>
+ <div className='col'>
+ <figure>
+ <img src="https://ars.els-cdn.com/content/image/1-s2.0-S1773224724002156-gr3_lrg.jpg" alt="Aufnahme LNP" style={{maxHeight: "200pt"}}/>
+ <figcaption>
+ <b>Figure. </b>
+ Endosomal escape vs degradation of LNP cargo at endocytosis.
+ </figcaption>
+ </figure>
+ </div>
+ <div className='col'>
+ <p>We optimized lipid nanoparticles (LNPs) as a robust delivery system to transport larger therapeutic cargo, such as Prime Editing mRNA, to lung epithelial cells via inhalation. LNPs were chosen over other delivery systems, like Adeno-associated viruses (AAVs), due to their superior cargo capacity and reduced immunogenicity. Our goal is to create a lung-specific LNP, named AirBuddy, capable of efficiently delivering of our Prime Editing components, referred to as PrimeGuide, to lung tissues through inhalation. This approach is designed to advance precision medicine by ensuring targeted delivery with minimal off-target effects.</p>
+ </div>
+ </div>
</Collapsible>
<Collapsible id="Col2" open={false} title="Challenges of working with LNPs">
<LoremShort/>
@@ -198,7 +225,7 @@ export function Description() {
<p>To optimize AirBuddy for pulmonary delivery, we collaborated extensively with several experts, including <a onClick={() => goToPagesAndOpenTab('weber', '/human-practices')}>Prof. Weber, Dr. Große-Onnebrink</a> and <a onClick={() => goToPagesAndOpenTab('tabid', '/human-practices')}>Dr. Kolonko</a> as medical experts, <a onClick={() => goToPagesAndOpenTab('kristian', '/human-practices')}>Prof. Dr. Müller</a>, <a onClick={() => goToPagesAndOpenTab('radukic', '/human-practices')}>Dr. Radukic</a>, Benjamin Moorlach and the Physical and Biophysical Chemistry working group as academic experts form Bielefeld University and FH Bielefeld as well as <a onClick={() => goToPagesAndOpenTab('corden', '/human-practices')}>Corden Pharma</a> and <a onClick={() => goToPagesAndOpenTab('rnhale', '/human-practices')}>RNhale</a> as industrial experts. Throughout the <a onClick={() => goToPagesAndOpenTab('tab-delivery', '/engineering')}>development process</a>, we tested two commercially available kits: the <strong>Cayman Chemical LNP Exploration Kit (LNP-102)</strong> and the <strong>Corden Pharma LNP Starter Kit #2</strong>. While the Cayman kit demonstrated limited transfection efficiency, the Corden Pharma formulation significantly enhanced cellular uptake in lung tissues. Building on this, we integrated the <strong>SORT LNP</strong> method based on Wang's research [1], making our nanoparticles lung-specific. Additionally, we employed a <strong>spray-drying technique</strong> by RNhale [2] to improve the stability of our LNP, ensuring that it withstands the inhalation process without degradation and by that, <strong>AirBuddy</strong> was born. </p>
<img src="https://static.igem.wiki/teams/5247/delivery/airbuddy.webp"></img>
<p>The SORT LNPs are especially suited for pulmonary delivery due to their capacity for precise organ targeting. Their structural stability is maintained during the delivery process, and the spray-drying approach significantly enhances their resilience, allowing the LNPs to remain intact throughout inhalation. This stability is crucial for the efficient delivery of mRNA into lung epithelial cells, where PrimeGuide can effectively perform genome editing. To evaluate the delivery efficiency, we transfected HEK293 cells using fluorescent cargo and quantified the results through FACS analysis.</p>
- <p>To ensure that AirBuddy meets the necessary standards for safety and efficacy, we conducted extensive <strong>characterization of the LNPs</strong> using techniques such as Zeta potential analysis, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Cryogenic Electron Microscopy (cryo-EM). These methods confirmed the uniformity, stability, and optimal size distribution of the nanoparticles. Furthermore, <strong>cytotoxicity assessments</strong>, including MTT and proliferation assays, demonstrated that our LNPs are biocompatible and do not impede cell growth or function by the incorporation of PEG and other ambivalent components. These findings reinforce AirBuddy's potential as a safe and effective tool for pulmonary delivery, with broad implications for gene therapies targeting lung diseases.</p>
+ <p>To ensure that AirBuddy meets the necessary standards for safety and efficacy, we conducted extensive <strong>characterization of the LNPs</strong> using techniques such as Zeta potential analysis, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Cryogenic Electron Microscopy (cryo-EM). These methods confirmed the uniformity, stability, and optimal size distribution of the nanoparticles. Furthermore, <strong>cytotoxicity assessments</strong>, including MTT and proliferation assays, demonstrated that our LNPs are biocompatible and do not impede cell growth or function by the incorporation of <a onClick={() => goToPagesAndOpenTab('Col1', '/engineering')}>PEG</a> and other ambivalent components. These findings reinforce AirBuddy's potential as a safe and effective tool for pulmonary delivery, with broad implications for gene therapies targeting lung diseases.</p>
</Subesction>
</Section>
<Section title="Our Vision" id="Our Vision">