My Placement Year in Switzerland

Increasingly, universities are offering integrated masters science degrees over bachelor degrees. These normally include an additional year of study and/or a placement year in industry or an academic research group. In this post I’ll tell you about the science I did on my placement in Switzerland and how it is linked to a major drug approval that happened a few months ago.

During my MChem placement year (2014/2015) at University of Strathclyde I worked as a Research and Development (R&D) intern for Corden Pharma Switzerland (CPS). They are a Contract Manufacturing Company of different Active Pharmaceutical Ingredients (APIs), Drug Products and Packaging Services. This means they produce various chemical products for pharmaceutical application for lots of different company clients.

CPSlogo
Picture caption: Corden Pharma logo with slogan “Experts taking care” Source: cordenpharma.com

The APIs produced at the CPS facility fall into a few categories: carbohydrates, lipids, peptides and other small molecules. At the start of my year there I worked on a short carbohydrate project where I produced a sugar-like compound for a big pharma client.

I spent the rest of my time working on a small molecule project for a slightly smaller company client. As part of a team of a few chemists I helped to make a large lipid-like molecule that helps deliver corrective pieces of nucleic acid into cells to treat genetically-linked diseases. This type of treatment is known as RNA interference (RNAi).

You may have heard of DNA, deoxyribose nucleic acid, a long double stranded molecule made up of individual nucleotides that contain the instruction manual for everything in our cells. There is another type of nucleic acid in the body called RNA, ribose nucleic acid. It possesses some structural differences to DNA such as the type of sugars and bases in the molecule and it exists as a single strand instead of a double strand.

DNA RNA
Picture caption: An partially unwound DNA molecule interacting with a single strand of mRNA. Source: Microsoft clipart

When a cell wants to carry out a particular function, the piece of DNA that codes for the protein that carries out that job is unwound by helicase enzymes. A temporary copy of that portion of DNA is made by RNA. This process is known as transcription.

This newly formed “messenger RNA” (mRNA) leaves the cell nucleus – the central region of the cell where DNA is stored – and travels to a ribosome that reads the instructions from the mRNA and builds the desired protein out of amino acids. Translation is the name given to this process.

protein translation
Picture caption: A green large green ribosome protein interacting with the RNA strand and building a new protein molecule. Blue tRNA molecules bring individual amino acids to the ribosome for building the protein. Source: clipart-library.com

But what if the protein being coded for is a harmful protein that leads to a disease symptom? The theory behind RNAi is that you can send foreign copies of RNA into cells to tell a ribosome to stop producing a particular protein.

These RNAs can tell the ribosome to stop making protein because they are complementary (similar in structure) to the original RNAs and so they bind together like a zip. This so-called interference could be used to treat diseases that are known to be caused by certain genes. Alnylam Pharmaceuticals have a great video that explains the science here.

RNAi
Picture caption: schematic summarising RNAi prcoess with natural blue mRNA and synthetic green small interfering RNA in moving around the cells. The siRNAs interact with the naturally produced mRNA leading to degradation of the mRNA. Source: the-scientist.com

RNAi won the 2006 Nobel Prize in Physiology/Medicine. It was awarded to Andrew Z. Fire and Craig C. Mello for successfully silencing a muscle gene in roundworms by injecting complementary RNA strands.

RNAi roundowrms
Picture caption: comparison of three green roundworms before and after treatment by RNA. Source: nobelprize.org

Their work showed that RNAi exists naturally in the body to regulate production of all proteins and can be done synthetically. The technique is now used by biologists around the world to shut down certain genes in cells and see the effect that it has. Researchers have also been trying to utilise it for medical use by giving patients complementary RNAs for disease-relevant proteins.

However, the body is usually very good at knowing where things should be in the body so it doesn’t expect to find bits of RNA outside of cells, e.g. in the bloodstream where most drugs end up.

The molecule I helped to make on my project allowed the attachment of these corrective RNAs to a big lipid. These big lipids then form nanoparticles (tiny bubbles) around the RNAs that help smuggle the RNAs across the cell membrane and into the cell where they can interact with ribosomes and shut down the production of harmful proteins.

I’m not allowed to tell you specifically how I made the molecule or what it looks like due to the confidentiality agreement I signed at the start of my placement year but it was wonderful to hear in August that the first RNAi therapy using this sort of chemistry was approved by the US Food and Drug Administration (FDA).

The treatment that was approved is called Patisiran (marketed as Onpattro by Alnylam Pharmaceuticals who developed it) and contains RNA strands that halt the formation of a protein called transthyretin. Transthyretin production leads to the symptoms of a genetic disorder called hereditary transthyretin (hATTR) amyloidosis. This is a rare disease where some 50,000 patients a year experience nerve damage due to the clumping of overproduced transthyretin.

Alnylam’s website says 51% of patients treated with Onpattro “experienced improvement in quality of life at 18 months” compared to 10% of patients who were treated with a placebo. This first-in-line treatment means that now one disease can be safely treated this way it might be possible to treat other genetically-linked diseases using RNAi.

It was really cool to see the science my project being approved as a new type of treatment which will hopefully pave the way for future RNAi therapies. While at times I was frustrated with the tricky chemistry I was doing on placement, I’ve been reminded by this approval that sometimes the goal of helping patients is met, which makes it worthwhile.

fiona matterhorn
Picture caption: Fiona in winter clothing standing in front of the famous triangular shaped Matterhorn mountain in snowy Zermatt, Switzerland.

Outside of the lab I enjoyed sampling different Swiss cheese and chocolate and travelling around the country on their first-class public transport system as well as further afield. While the country is very expensive, it’s a beautiful place to live with the Alps and picturesque old towns. I enjoyed being back last weekend and showing my friend Emily around – check out my Instagram for a post about her job as a consultant process engineer.

I learned a lot of chemistry (and Swiss German) on my placement and would thoroughly recommend taking any opportunity to gain industrial experience during your degree to give a taste of what life as a scientist is like.

Have you come across RNAi? Does it seem like a viable way to treat diseases? Have you visited Switzerland? Let me know in the comments below.

I kept a photo-a-day blog on blipfoto during my time in Switzerland and wrote a few blog posts about living en Suisse, one of which was reposted on globalgraduates.com.

 

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