Are even better vaccines on the hoRNAzon?

To vaccinate our bodies against lethal diseases, like smallpox, we need to have the pathogen injected into our bodies in order to teach our immune system how to recognise it and fight it. Obviously we cannot use a perfectly healthy microbe for this injection as this would give a result quite opposite to intention. Therefore, many vaccines are made of bacteria or viruses that were killed prior to injection. Killed pathogens can not do any harm to our bodies, but are good enough to teach our immune system what they look like, so that should their healthy counterparts infected us in the future, our white blood cells are fully equipped to fend them off almost immediately. But for some vaccines the immune response isn’t quite as strong as during an actual infection with the living version of the bug.
Leif Sander and colleagues went for a hunt for what it is about living bacteria that makes them more irritating to our immune system. To their (and mine) great surprise the part of bacteria that seems to be doing a big part of the job, was RNA, a kind of molecule present in all living cells. Firstly, they analysed killed bacteria for several kinds of life-building blocks (including DNA and RNA) and found that RNA was the only one that was rapidly destroyed when bacteria were being killed. Their subsequent experiments were quite straightforward – they treated immune cells with either living bacteria, dead bacteria, or dead bacteria mixed with intact bacterial RNA, and measured how aggressively immune cells would react to these treatments. They also used the three mixtures to inject living animals to see how they would response to such vaccinations. In both cases – immune cells cultured in vtiro, and in living animals – the immune response was strong for living bacteria, weaker for dead bacteria, and strong again (or sometimes even stronger) for dead bacteria mixed with bacterial RNA.
Obviously this is the first observation of such kind, but the potential implications of it might be really beneficial. Often vaccines don’t have a 100% success rate, i.e. not all vaccinated people are protected from the actual disease. If in future, we’d be able to develop vaccines which would contain a mix of dead bugs with their intact RNA, we might be able to provide much more successful protection of the population. Watch this field! I certainly will.

1. Detection of prokaryotic mRNA signifies microbial viability and promotes immunity

Don’t miss! Totally ethical embryonic stem cells! Now 100 times more for 4 times less!

This news was published already on April 8^th this year, but I have only recently come across it.

Induced pluripotent stem (iPS) cells have been a very sexy topic since they were first generated in 2006. They are very much like embryonic stem cells, but their generation involves no embryo killing and thus they completely circumvent the whole ethical debate. To generate these cells, in a nutshell, scientists took some fibroblasts (adult cells) and treated them with retroviral vectors (a sort of molecular syringes) which carried genes that can make a cell go into embryonic – or pluripotent – state. This way they reprogrammed the fibroblasts to return to embryonic-like state. But the efficiency of this procedure was extremely low, as only about 0.02% of human fibroblasts turned into iPS cells (1). And when you think about it, it’s not much of a surprise. To reprogram a cell, you need three or four genes, which is three or four separate viral vectors. If a viral vector infects only, say, 20%, of a cell population, then two vectors will infect only 20% of that 20%, and so on. On top of that, not all infected cells will give in to the effect of the introduced gene. In the end, you end up with only a small fraction of cells that both took up all the genes and underwent successful reprogramming.

In the publication that I am going to comment on here (2), the scientists took a slightly different approach. They also used the retroviral vector as a gene delivery tool. However, instead of four, there were able to use only one retroviral vector. Normally, it’s hard to fit many genes into one vector, but these guys used only two – not three or four – genes. And on top of that, they were a very different kind of genes coding so-called miRNA. Now, unlike other genes, miRNAs don’t get translated into proteins but they can be very powerful when it comes to regulating levels of other proteins. And on top of that – miRNA genes are far smaller than protein genes, so it was not so much of a challenge to fit two of them into one vector. Effectively, using this technique they were able to generate iPS cells with about 100-fold higher efficiency!

This is pretty exciting but still pretty recent. If it is going to repeated by other researchers, chances are, this will become the standard protocol for generation of iPS cells. Which in turn hold a great promise for serving as good in vitro models of genetic disorders and maybe – in future – for personalised regenerative medicine.

1. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. 
2. Highly Efficient miRNA-Mediated Reprogramming of Mouse and Human Somatic Cells to Pluripotency.

Hello world! Micro-world and nano-world!

Hi,
my name's Andrzej. I do research in life sciences, which is mainly pipetting, trying, succeeding and failing to discover new things. But apart from my own work, I try to stay on top of what other scientists, in other areas have discovered, and how it might make this world a better place. And I thought maybe I could share it. So here it is - my science tick. You can think of it as a moment of science, or science that makes me tick (and NOT a scientific insect that bites you and causes Lyme disease).
Hope you enjoy it!