A Percutaneous Transcatheter Gene Delivery Patch

October 7, 2015
By Justin Cho   Flintridge Preparatory  Senior

By Justin Cho
Flintridge Preparatory

Atrial Septal Defect (ASD) is a congenital heart disease of which there is a septum in between the right and left atrium.

As babies develop during pregnancy, there are normally holes in the chamber walls that should close after birth. However, due to gene mutations, these holes could potentially not close up. The septum causes deoxygenated blood to mix with oxygenated blood; it results in damage in the blood vessels and higher pressure in the lungs.

Nearly 2,000 people are diagnosed with this defect every year.

The current methods used to treat this defect are cardiac cathereterization or open-heart surgery.

This past summer, I had the opportunity to get hands on experience and do research at Stanford’s Cardiovascular Surgical Skills Summer Internship (CSSSI). Handed the task of researching an alternative, non-invasive solution to treating ASD, my group and I created Myogene: A Percutaneous Transcatheter Gene Delivery Patch.

With new mRNA technology available, biological companies, such as Moderna, have found that instead of transcribing DNA to RNA to make cellular proteins, we can bypass one step and insert mRNA transcripts to directly yield protein in a more efficient manner.

The first step in this process is to induce cardiomyocyte proliferation. The cell naturally needs growth factors (Insulin Growth Factor-1, Fibroblast Growth Factor 2, Glycoprotein 130) in order to divide, and by adding extraneous amounts via our technology, we are able to induce proliferation by speeding up the division process.

However, the first problem that comes to mind during cell proliferation is the possibility of cancer. In order to eliminate this problem, we use extracellular matrix proteins to provide an anchorage.

One of the main molecular techniques that Myogene uses is the Biotin-Streptavadin system. Biotin and Streptavidin have a very high affinity towards each other.

The Wadsworth Center has done an experiment regarding directed cell growth by labeling laminin and fibronectin with biotin, hence explaining our idea’s rationale. Myogene’s final step consists of mixing a solution of cationic lipids with our desired anionic mRNA to form a complex called a lipoplex. Our lipoplex could then fuse with cardiac myocyte cells and endocytose the mRNA contents, which promote cell growth and division.

By applying this technology, Myogene has the potential to treat ASD in a more efficient and safer manner. With the advances in technology of bypassing the Central Dogma, the future for mRNA processing is bright in the field of medicine.



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