<h4>Current HemA treatment consists of regular injections with Factor VIII protein.</h4>
<p>
And, even though this approach has its benefits: it can be done by the patient themselves and there are possibilities for an implantable port for easy administration, there are still some limitations.
And, even though this approach has its benefits - it can be done by the patient themselves and there are possibilities for an implantable port for easy administration - there are still some limitations.
On top of that, a Haemophilia patient has to make frequent injections - every 48 hours - to keep their FVIII levels on a normal level.
The frequent injections are in part the result of the high clearance of factor VIII from the circulation with a half-life of 10-12 hours.
This causes the factor VIII concentration in the blood to fluctuate a lot, spiking up after injection, then quickly going down until the next injection.
Currently, there are multiple engineered recombinant factor VIII products available, but these are way more expensive than the cheapest variety of FVIII, which is purified from blood products and already has an annual cost of $300,000!
</p>
...
...
@@ -121,6 +131,20 @@
When the nanoparticle reaches its target in the body, the cells will take it up into a lysosome and break the LNP preserving the genetic sequence inside.
After that, the cell produces the protein factor VIII from the mRNA and releases it into the blood.
</p>
<p>
Ionizable lipids are crucial for LNP preparation, and they provide effective mRNA encapsulation, as well as safe LNP delivery in the body.
Their role is crucial, since they change their charge due to protonation under acidic pH (become positively charged), or deprotonation under the neutral pH (become not charged).
This feature makes it possible to encapsulate the mRNA more efficiently, as well as their safe delivery in a blood neutral pH environment.
</p>
<p>
The LNPs are delivered via the nasal spray delivery system by the use of hydrogel, composed of poloxamer 407, poloxamer 188, NA-CMC, and almotriptan.
This hydrogel provides a biphasic release pattern: the quick release for 30 minutes (this provides an acute release of a medicine upon administration) and a sustained release for a 5 hour period (this maintains a loading dose of the medicine).
</p>
<p>
LNPs are administered into the bloodstream to travel to the liver and target LSECs with the help of surface proteins.
Once inside the cells, the LNPs will release the mRNAs, leading to the production of coagulation factor VIII.
This approach enables patients to produce their own coagulation factor VIII, eliminating the need for frequent injections of plasma-derived or recombinant proteins.
</p>
<divclass="center-div">
<imgsrc="https://static.igem.wiki/teams/5342/images/home/infinityf-method.webp"alt="Diagram that explains the InfinityF delivery process"class="main-img">
</div>
...
...
@@ -138,12 +162,14 @@
The factor VIII mRNA is produced with in vitro transcription using factor VIII pcDNA as a template.
Our ionizable lipid nanoparticles contain synthetic lipids as well as an ionizable lipid, which is essential for the release of the mRNA in the cells.
</p>
<!--<h5>Frequent Injections</h5>-->
<h5>Frequent Injections</h5>
<p>
While the current Hemophilia medicine has a high clearance with a half-life of 10-12 hours, thanks to the biphasic release pattern of hydrogel, applied in InfinitiF∞, provides for a temporarily release of the medicine, prolonging the time of its circulation in the bloodstream, and providing patient with a longer duration of effect of the medicine.
</p>
<h5>Concentration Spikes</h5>
<p>
Production of protein from mRNA occurs gradually and not in all cells at the same time, spreading out the high concentration spike that occurs after injection of FVIII. €
Production of protein from mRNA occurs gradually and not in all cells at the same time, spreading out the high concentration spike that occurs after injection of FVIII.
</p>
<!--<h5>High Clearance</h5>-->
<h5>Cost</h5>
<p>
Costs are very important when speaking about medical treatment.
...
...
@@ -153,7 +179,7 @@
</p>
<h3>We are the first iGEM team in Radboud’s History</h3>
<h4>We are the Radboud iGEM Team!</h4>
<h4>We are the FIRST Radboud iGEM Team!</h4>
<p>
The Radboud iGEM team was started by a group of enthusiastic students that were looking to broaden their horizon and start something new.
We hope to introduce the iGEM competition to Radboud university while also putting Radboud university on the map within the iGEM competition.
...
...
@@ -163,12 +189,16 @@
With our efforts, we hope to pave the way for future Radboud iGEM teams.
</p>
<p>
We are beyond excited to showcase InfinityF as the first team to represent Radboud University within the iGEM competition, and it is with passion and determination that we say:
We are beyond excited to showcase InfinityF∞ as the first team to represent Radboud University within the iGEM competition, and it is with passion and determination that we say:
</p>
<h4style="font-weight: bold; font-style:italic; text-align:center; color:#e3000b">Let’s synthesize a better future together!</h4>
<li>Chen, Chun-Yu, et al. “Treatment of Hemophilia a Using Factor VIII Messenger RNA Lipid Nanoparticles.” Molecular Therapy - Nucleic Acids, vol. 20, 5 June 2020, pp. 534–544, www.sciencedirect.com/science/article/pii/S2162253120301062, https://doi.org/10.1016/j.omtn.2020.03.015.</li>
<li>Salen, Philip, and Hani M. Babiker. “Hemophilia A.” PubMed, StatPearls Publishing, 2024, www.ncbi.nlm.nih.gov/books/NBK470265/#:~:text=Hemophilia%20A%20is%20the%20most.</li>
