diff --git a/src/App/App.css b/src/App/App.css
index 57f872a772723e5c5830c2ed6cc3a0829334901b..91e1bc69de2cf18e4dcec94ccc5149a5da148fdb 100644
--- a/src/App/App.css
+++ b/src/App/App.css
@@ -3895,6 +3895,7 @@ figure img{
justify-content: center;
margin-top: var(--big-margin) !important;
margin-bottom: var(--big-margin) !important;
+ padding: 0 !important;
}
figure {
diff --git a/src/components/Complex-svg.tsx b/src/components/Complex-svg.tsx
index e09ec6e2328861bdb40ea32ff9d2a1399a7e3d33..912c6f261c18eb430aa3ebcc1b301093b5e4c0f2 100644
--- a/src/components/Complex-svg.tsx
+++ b/src/components/Complex-svg.tsx
@@ -9,6 +9,8 @@ export default function SVG(){
overflow="hidden"
version="1.1"
id="svg367"
+ width={"500"}
+ height={"100%"}
inkscape:export-ydpi="9.5955524"
xmlns="http://www.w3.org/2000/svg">
<defs
diff --git a/src/contents/description.tsx b/src/contents/description.tsx
index 8a8b7d9d5a044c7f4b140ba9a64b825a3a2e5eff..3d2893ca8d2b38b2010925d14907021e5d044516 100644
--- a/src/contents/description.tsx
+++ b/src/contents/description.tsx
@@ -43,7 +43,12 @@ export function Description() {
<p>As we explored Cystic Fibrosis further, we were struck by how widespread it is, being the most common genetic disorder in Germany. Approximately 70% of those with CF are specifically affected by the F508del mutation <SupScrollLink label="1"/> . This mutation is the most prevalent and well-studied of the thousands of genetic variations that cause CF, making it an important focus of research and intervention. In fact, about 90% of Europeans and individuals of European descent with CF have at least one F508del allele <SupScrollLink label="2"/><sup>,</sup><SupScrollLink label="3"/>. This widespread prevalence highlighted the significance of our project—not just for our friend, but for the thousands of others affected by this mutation across Europe and beyond. </p>
</div>
<div className="col" >
- <img className="img" src="https://static.igem.wiki/teams/5247/photos/other/max-bild.webp"/>
+ <OneFigure
+ pic1="https://static.igem.wiki/teams/5247/photos/other/max-bild.webp"
+ alt1=""
+ description="Philiiiip"
+ num="?"
+ />
</div>
</div>
<p>By focusing on the F508del mutation, we also hope to contribute valuable insights to the global cystic fibrosis community. Although this mutation is most common in European populations, it is also found in other regions around the world <SupScrollLink label="4"/><sup>,</sup><SupScrollLink label="5"/>. Our research could thus help inform treatment strategies and health policies on an international scale. </p>
@@ -52,7 +57,6 @@ export function Description() {
</Section>
<Section title="Cystic Fibrosis" id="Cystic Fibrosis">
<Subesction title="Overview" id="Cystic Fibrosis1">
- <div className="row align-items-center">
<p data-aos="zoom-y-out" >Cystic Fibrosis (CF) is a common life-limiting genetic disorder, particularly affecting the Caucasian population, with approximately <b>162,400 people worldwide</b> living with the condition <SupScrollLink label="7"/> . Statistically, about <b>one in every 3,300</b> white newborns is born with CF <SupScrollLink label="8"/> . And according to the German Cystic Fibrosis Registry, the average life expectancy for children born with CF in 2021 was around 57 years <SupScrollLink label="9"/> , highlighting the severe and life-shortening nature of the disease. </p>
<p>The modern understanding of CF dates back to 1922 when Dr. Dorothy Andersen, a pediatric specialist, first described the disease and coined the term "Cystic Fibrosis" <SupScrollLink label="10"/> . In Germany, it is commonly known as "Mukoviszidose," derived from the Latin words meaning "mucus" and "viscous" <SupScrollLink label="10"/> , emphasizing the characteristic thick, sticky mucus that defines the condition <SupScrollLink label="11"/><sup>,</sup><SupScrollLink label="12"/>. </p>
<p>Genetic research has identified over 1,700 mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, with the F508del mutation being the most common, affecting about 70% of CF patients. This mutation prevents the proper folding of the CFTR protein, significantly impairing its function <SupScrollLink label="13"/> . </p>
@@ -71,11 +75,13 @@ export function Description() {
<p><b>Class IV, V</b> and <b>VI</b> mutations are rare. These mutations result in the production of unstable or inefficient CFTR proteins, which do not function adequately and are produced in insufficient numbers.</p>
</Collapsible>
<p>The prevalence of CF varies globally, with higher concentrations of cases in Europe, North America, and parts of Oceania. This geographic variation underscores the need for regionally tailored healthcare solutions. </p>
- </div>
- <div className="casettecontainer">
- <img src="https://static.igem.wiki/teams/5247/charts-maps/cfper10-000.png"></img>
- </div>
-
+ <OneFigure
+ pic1="https://static.igem.wiki/teams/5247/charts-maps/cfper10-000.png"
+ alt1=""
+ num="?"
+ description="Philip, mach hier eine Description rein"
+ />
+
<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>
<p>Although there is currently no cure for CF, patients must manage the disease throughout their lives, relying on treatments that alleviate symptoms but do not address the root cause. This lifelong management imposes significant financial burdens on affected families and healthcare systems, particularly in regions with a high prevalence of CF <SupScrollLink label="15"/> . In recent years, <b>CFTR modulators</b>, which target the underlying genetic defect, have offered new hope for many patients. </p>
</Subesction>
@@ -92,6 +98,7 @@ export function Description() {
</ul>
<div className="row align-items-center">
<div className="col">
+ {/* This one this has tp stay a figure and not be a OneFigure */}
<div className="figure-wrapper">
<figure>
<div className="col gif-wrapper">
@@ -197,6 +204,7 @@ export function Description() {
<li><b>Flap Resolution and Final Editing</b>: In some cases, an additional nick (seen in the PE3/PE5 systems in the image) is introduced in the non-target DNA strand to promote repair and favor the incorporation of the edit. This step increases the efficiency of Prime Editing by ensuring that the newly edited strand is preferentially used during the cell's DNA repair process. The mismatch repair (MMR) system of the cell also plays a role in determining whether the edit is retained or reverted to the original sequence. For systems like PE4 and PE5, inhibition of the mismatch repair system (e.g., by MLH1dn) further promotes the integration of the desired edit.</li>
<li><b>Final outcome</b>: Once the unedited flap is degraded and the new sequence is integrated, the cell completes the repair, and the edit becomes permanently incorporated into the DNA. As shown in the diagram, the result is a successful genetic modification, where the new, corrected sequence replaces the original faulty sequence.</li>
</ol>
+ {/* This figure has to stay this way */}
<figure>
<img className="gif-wrapper" src="https://static.igem.wiki/teams/5247/project-description/prime-editing-animation-10fps.gif"/>
<figcaption>
@@ -209,11 +217,22 @@ export function Description() {
</InfoBox>
<p>However, the Prime Editing complex is relatively large, posing challenges for therapeutic delivery<SupScrollLink label="3"/>. Additionally, Prime Editing has been shown to be relatively inefficient in terms of gene editing rates, which could limit its therapeutic utility<SupScrollLink label="4"/>. Our project aims to enhance the Prime Editing approach by miniaturizing its components and enhancing its efficiency, as well as precision. </p>
<p>As shown in the image, we developed two potential configurations for Prime Guide, each using a different nickase: one based on the Fanzor (nSpuFz1) nickase and the other on a CasX (nPlmCasX) nickase. Both configurations are designed to improve the precision and stability of the Prime Editing system. The pegRNA scaffold, reverse transcriptase (PE6c), and primer binding site (PBS/RTT) work together in both systems to introduce precise edits, with the La(1-193) enhancing stability and function.</p>
+
+
+ <div className="figure-wrapper">
+ <figure>
<div className="row">
<div className="col">
+
<img className="img" src="https://static.igem.wiki/teams/5247/project-description/primeguide.png"/>
</div>
- <div className="img-right img-half col"><PrimeEditingComplex/></div>
+ <div className="col"><PrimeEditingComplex/></div>
+ </div>
+ <figcaption>
+ <b>Figure ???: </b>
+ Philiiiip
+ </figcaption>
+ </figure>
</div>
<p>To develop our innovative Prime Editing system, Prime Guide, we worked closely with several leading experts in the field. Among them were Mattijs Bulcaen, Makato Saito, Dr. Hammer, Jan-Phillipp Gerhard and Prof. Kristian Müller, whose insights helped guide our decisions. Prime Guide is a highly specialized Prime Editing complex, designed to target the F508del mutation in cystic fibrosis with precision and efficiency. </p>
<p>Our Prime Guide system consists of carefully selected components, each optimized for its role. For the nickase, we chose between SpuFz1 and CasX nickases due to their smaller size and structural advantages, which suggest increased stability for the pegRNA within the Prime Editing complex. Smaller nickases also provide benefits in terms of overall efficiency and ease of delivery, aligning with the compact design we aimed for.</p>
@@ -240,16 +259,32 @@ export function Description() {
<p>The PreCyse-Cassette is engineered to provide maximum flexibility for the construction of the Prime Editing systems. It includes BsaI und SapI cloning sites, allowing easy insertion and exchange of essential components like a nickase and reverse transcriptase, fundamental for Prime Editing. Additionally, it incorporates a cloning site for the guide RNA, ensuring seamless integration and adaptation to various target sequences.</p>
<p>Moreover, the PreCyse-Cassette contains several advanced features designed to enhance system performance. The architecture of this cassette is based on a combination of the PE4 and PE7 systems, providing the presence of the LA motif and MLH1dn. Thus allowing an increased functionality and editing efficiency, while the CMV and T7 promoters ensure high expression levels across different systems. These features make the cassette universally applicable to a wide range of Prime Editing contexts, enabling users to effortlessly clone their desired components—nickase, reverse transcriptase, and guide RNA—without the need for complex modifications.</p>
<p>With this PreCyse-Cassette, researchers can easily set up and test their Prime Editing systems, bypassing much of the laborious cloning work traditionally associated with these setups. The cassette provides an efficient and versatile platform for experimenting with and refining Prime Editing applications, forming the ideal backbone for PrimeGuide and beyond.</p>
- <img className="img" src="https://static.igem.wiki/teams/5247/fanzor/kassettemech.webp"/>
+ <OneFigure
+ pic1="https://static.igem.wiki/teams/5247/fanzor/kassettemech.webp"
+ alt1=""
+ description="Phiiilip"
+ num="????"
+ />
</Subesction>
<Subesction title="Delivery" id="Approach2">
<div className='row align-items-center'>
<div className='col'>
- <img src="https://static.igem.wiki/teams/5247/delivery/sort-lnp-ohne-beschriftung.webp"/>
+ <OneFigure
+ pic1="https://static.igem.wiki/teams/5247/delivery/sort-lnp-ohne-beschriftung.webp"
+ alt1=""
+ description="Phiiilip"
+ num="????"
+ />
</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>
- <img src="https://static.igem.wiki/teams/5247/delivery/airbuddy.webp" style={{maxHeight: "80pt"}}/>
+ <OneFigure
+ pic1="https://static.igem.wiki/teams/5247/delivery/airbuddy.webp"
+ alt1=""
+ description="Phiiilip"
+ num="????"
+ />
+ <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>
@@ -265,13 +300,12 @@ export function Description() {
<H4 text="Role of surface modifications in targeting" id="text" />
<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 2. </b>
- Endosomal escape vs degradation of LNP cargo at endocytosis <SupScrollLink label="4"/> .
- </figcaption>
- </figure>
+ <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>}
+ />
</div>
<div className='col'>
<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 <SupScrollLink label="4"/> .</p>
@@ -294,7 +328,12 @@ export function Description() {
<br/>
<div id="airbuddy-hook" className='row align-items-center'>
<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('kolonkofirst', '/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>, <a onClick={() => goToPagesAndOpenTab('moorlach', '/human-practices')}>Benjamin Moorlach</a> and the <a onClick={() => goToPagesAndOpenTab('biophysik', '/human-practices')}>Physical and Biophysical Chemistry working group</a> as academic experts from 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={() => goToPageWithTabAndScroll({tabId:'tab-delivery', path: '/engineering', scrollToId: "delivery-header"})}>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 showed good non-lung-specific transfection efficiency, the Corden Pharma formulation also proved not to be the right approach. Building on this, we integrated the <strong>SORT LNP</strong> method based on Wang's research<SupScrollLink label="1"/> , making our nanoparticles lung-specific. Additionally, we employed the <strong>chitosan-complexation of the therapeutic cargo</strong> to improve the stability of our LNP, ensuring that it withstands the inhalation process without degradation. Moreover, further stabilization approaches including the employment of the <strong>spray-drying technique</strong> in cooperation with RNhale<SupScrollLink label="2"/> are in the pipeline. This improved stability is crucial for the efficient delivery of mRNA into lung epithelial cells, where PrimeGuide can effectively perform genome editing.</p>
- <img src="https://static.igem.wiki/teams/5247/delivery/big-plan-inhalation-teil-del.webp"/>
+ <OneFigure
+ pic1="https://static.igem.wiki/teams/5247/delivery/big-plan-inhalation-teil-del.webp"
+ alt1=""
+ description="Philiiiiip"
+ num="?"
+ />
</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>
</Subesction>