diff --git a/src/contents/description.tsx b/src/contents/description.tsx index 9be6a8caf3b66912ce45a61fdacb455567fade3b..ddbb09ce4e3833493e5ff8a361bc87eedfe95346 100644 --- a/src/contents/description.tsx +++ b/src/contents/description.tsx @@ -46,8 +46,8 @@ export function Description() { <OneFigure pic1="https://static.igem.wiki/teams/5247/photos/other/max-bild.webp" alt1="" - description="Picture from our interview with Max" - num="?" + description="Picture from our interview with Max." + num="1" /> </div> </div> @@ -63,9 +63,9 @@ export function Description() { <p>The CFTR protein regulates the flow of chloride ions across the membranes of cells in the lungs, digestive system, and other organs. This ion flow is essential for drawing water into surrounding tissues, which helps maintain the proper hydration and consistency of mucus. In patients with CF, the disruption of this process prevents sufficient water from entering the mucus, making it abnormally thick and sticky. The accumulation of this mucus leads to an obstruction of airways and digestive ducts, resulting in chronic lung infections, inflammation, impaired digestion, and malnutrition<SupScrollLink label="14"/> . </p> <OneFigure pic1="https://static.igem.wiki/teams/5247/project-description/lung-ephitel-biorender.png" - num={1} + num={2} bg="white" - description="Lung ephitelium of human with correct CFTR expression (left) and Cystic Fibrosis (right)" + description="Lung ephitelium of human with correct CFTR expression (left) and Cystic Fibrosis (right)." alt1="Lung ephitelium of human with correct CFTR expression (left) and Cystic Fibrosis (right)." /> <Collapsible id="classes-mutations-collapsible" title="Different classes of mutations"> @@ -79,9 +79,9 @@ export function Description() { <OneFigure pic1="https://static.igem.wiki/teams/5247/charts-maps/cfper10-000.png" alt1="" - num="?" + num="3" bg="white" - description="Global distribution of cystic fibrosis cases: Countries are color-coded based on the number of reported cases, highlighting regional prevalence patterns" + description="Global distribution of cystic fibrosis cases: Countries are color-coded based on the number of reported cases, highlighting regional prevalence patterns." /> <p>CF is often diagnosed early through newborn screening programs, which detect elevated levels of immunoreactive trypsinogen (IRT). A positive result typically leads to a sweat test, the gold standard for diagnosing CF, which measures the concentration of chloride in sweat. </p> @@ -106,7 +106,7 @@ export function Description() { <div className="col gif-wrapper"> <img className="CFTR-gif" src="https://static.igem.wiki/teams/5247/fanzor/cftr-wt.gif"></img> </div> - <figcaption> <b>Animation 1:</b> Model of a functional CFTR Enzyme.</figcaption> + <figcaption> <b>Animation 1.</b> Model of a functional CFTR protein.</figcaption> </figure> </div> <H4 text="Function of CFTR" id="function-cftr" /> @@ -210,8 +210,8 @@ export function Description() { <figure> <img className="gif-wrapper" src="https://static.igem.wiki/teams/5247/project-description/prime-editing-animation-10fps.gif"/> <figcaption> - <b>Figure 4: </b> - Illustration of the Prime Editing process and its possible outcomes + <b>Animation 2. </b> + Illustration of the Prime Editing process and its possible outcomes. </figcaption> </figure> <p>Overall, there are many different Prime Editing systems with a variety of components and complexity, starting from PE2 up to PE7. Possible edits could integrate substitutions, inserts and deletions in the range of one base up to hundreds of nucleotides, with gradually decreasing editing efficiency. Therefore Prime Editing technology allows targeted modifications of specific genes. </p> @@ -231,8 +231,8 @@ export function Description() { <div className="col"><PrimeEditingComplex/></div> </div> <figcaption> - <b>Figure ???: </b> - Illustration of our newly designed Prime Editors, "PrimeGuide" + <b>Figure 4. </b> + Illustration of our newly designed Prime Editors, "PrimeGuide". </figcaption> </figure> </div> @@ -265,7 +265,7 @@ export function Description() { pic1="https://static.igem.wiki/teams/5247/fanzor/kassettemech.webp" alt1="" description="Schematic diagram of the constructed plasmid containing our Reporter System" - num="????" + num="5" /> </Subesction> <Subesction title="Delivery" id="Approach2"> @@ -274,25 +274,22 @@ export function Description() { <OneFigure pic1="https://static.igem.wiki/teams/5247/delivery/sort-lnp-ohne-beschriftung.webp" alt1="" - description="3D Figure of AirBuddy" - num="????" + description="3D Figure of our optimized SORT LNP called AirBuddy." + num="6" /> </div> <div className='col'> <p>We optimized 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 was to create a spray-dried lung-specific LNP named</p> - <OneFigure - pic1="https://static.igem.wiki/teams/5247/delivery/airbuddy.webp" - alt1="" - description="Name of our LNP" - num="?" - /> + <figure> + <img className="gif-wrapper" src="https://static.igem.wiki/teams/5247/delivery/airbuddy.webp"/> + </figure> <img src="" style={{maxHeight: "80pt"}}/> <p>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 id="Col1" open={false} title="LNPs explained"> - <H4 text="What are LNPs" id="text" /> - <p>Lipid nanoparticles are small, spherical structures made of lipids that serve as delivery vehicles for therapeutic molecules, such as RNA, DNA, or drugs. They protect their cargo from degradation, enhance cellular uptake, and are widely used in mRNA vaccines and gene therapy due to their efficiency and biocompatibility.</p> + <H4 text="What are LNPs?" id="text" /> + <p>Lipid nanoparticles, short LNPs, are small, spherical structures made of lipids that serve as delivery vehicles for therapeutic molecules, such as RNA, DNA, or drugs. They protect their cargo from degradation, enhance cellular uptake, and are widely used in mRNA vaccines and gene therapy due to their efficiency and biocompatibility.</p> <H4 text="LNPs and their impact on modern medicine" id="text" /> <p>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 LNPs typically ranges from 50 to 200 nm in diameter, making them incredibly small - about 1,000 times thinner than a human hair <SupScrollLink label="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 <SupScrollLink label="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 <SupScrollLink label="9"/> .</p> @@ -307,8 +304,8 @@ export function Description() { <OneFigure pic1="https://ars.els-cdn.com/content/image/1-s2.0-S1773224724002156-gr3_lrg.jpg" alt1="Aufnahme LNP" - num={2} - description={<span> Endosomal escape vs degradation of LNP cargo at endocytosis <SupScrollLink label="4"/></span>} + num={8} + description={<span> Endosomal escape vs degradation of LNP cargo at endocytosis <SupScrollLink label="4"/>.</span>} /> </div> <div className='col'> @@ -335,8 +332,8 @@ export function Description() { <OneFigure pic1="https://static.igem.wiki/teams/5247/delivery/big-plan-inhalation-teil-del.webp" alt1="" - description="Schematic representation our LNP-based drug delivery system" - num="?" + description="Schematic representation our LNP-based drug delivery system." + num="9" /> </div> <p>To evaluate the <strong>delivery efficiency</strong>, we transfected HEK293 and CFBE41o- cells using fluorescent cargo and quantified the results through flow cytometry analysis. We also ensured that AirBuddy meets the necessary standards for safety and efficacy since we conducted extensive <a onClick={() => goToPageAndScroll ('In-Depth Characterization of LNPsH', '/materials-methods')}> characterization of the LNPs </a>using physicochemical techniques such as Zeta potential analysis, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and Cryogenic Electron Microscopy (cryo-EM). These methods confirmed the stability and optimal size distribution of the nanoparticles. Furthermore, <strong>cytotoxicity assessments</strong> including MTT and proliferation assays demonstrated that our LNPs are biocompatible despite the incorporation of <a onClick={() => goToPageWithTabAndCollapsible({tabId:'tab-delivery', path: '/engineering', collapseId: "Col1"})}>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> @@ -347,8 +344,8 @@ export function Description() { <p>We have successfully demonstrated a <b>proof of concept</b> for our gene therapy approach targeting Cystic Fibrosis. In initial experiments, HEK cells carrying a 3-base deletion analogous to the <i>F508del</i> mutation were transfected with our prime editing complex. The results met our expectations, confirming the viability of our approach for precise gene correction. Based on these findings, we optimized the prime editing complex, leading to the creation of <b>PrimeGuide</b>, a more compact and efficient editing tool. </p> <p>Central to our <b>delivery system</b> is <b>AirBuddy</b>, a lung-specific lipid nanoparticle designed to stabilize and protect the prime editing complex during transport to lung epithelial cells. <b>AirBuddy</b> ensures that the protein complex is delivered specifically to lung cells, enhancing the efficiency of the gene-editing process. By modifying the lipid nanoparticle with protective features, we achieved increased stability, ensuring effective delivery to the target cells. </p> <p>We further optimized the prime editing fusion protein, <b>PrimeGuide</b>, to streamline its components, resulting in a smaller and more efficient prime editing complex. This improvement significantly enhances the precision of the gene editing process, reducing off-target effects and increasing the overall success of mutation correction. </p> - <p>In subsequent experiments, <b>HEK and lung (CFBE41o-)cells</b> carrying the CFTR <i>F508del</i> mutation were successfully <b>transfected</b> with the optimized prime editing complex. Our results indicated successful correction of the mutation, confirming the potential of our approach for treating Cystic Fibrosis. </p> - <p>Additionally, we explored <b>downstream applications</b>. Primary cell cultures were treated with lipid nanoparticles to introduce a reporter RNA. </p> + <p>In subsequent experiments, <b>HEK293 and CFBE41o- cells</b> carrying the CFTR <i>F508del</i> mutation were successfully <b>transfected</b> with the optimized prime editing complex. Our results indicated successful correction of the mutation, confirming the potential of our approach for treating Cystic Fibrosis. </p> + <p>Additionally, we explored <b>downstream applications</b>. Primary cell cultures were treated with lipid nanoparticles to introduce a reporter RNA and Patch Clamp measurements were explored as a validation method.</p> </Section> <Section title="Our Vision" id="Our Vision"> <p>At <b>PreCyse</b>, we envision a future where gene therapy for Cystic Fibrosis (CF) is as simple and user-friendly as using an inhaler. Our goal is to develop a fully integrated Prime Editing system, <b>PrimeGuide</b>, delivered via a cutting-edge lipid nanoparticle (LNP) platform, <b>AirBuddy</b>. The therapy would allow patients to inhale the therapeutic complex, targeting the underlying genetic mutation that causes CF—specifically, the F508del mutation in the CFTR gene. </p> @@ -358,8 +355,8 @@ export function Description() { <p>Ultimately, our vision is to create a therapeutic approach that not only offers a cure that is safe and efficient but also maximizes convenience for the patient. With an easy-to-use inhaler, patients could administer their treatment with minimal disruption to their daily lives, inhaling the gene therapy in just a few breaths, leaving the rest of the process to the science we've built into PreCyse. By reducing the frequency of administration and simplifying the delivery method, we aim to make gene therapy for Cystic Fibrosis both accessible and practical for patients around the world. </p> <OneFigure pic1="https://static.igem.wiki/teams/5247/delivery/big-plan-inhalation-del-mech.webp" - num={4} - description="Illustration of our path from final product to prime editing in lung epithelial cells" + num={10} + description="Illustration of our path from final product to prime editing in lung epithelial cells." alt1="Illustration of our path from final product to prime editing in lung epithelial cells." /> </Section>