Archive for April, 2010

Targeted delivery of siRNA by nanoparticles in humans

Sunday, April 18th, 2010

An important milestone in the use of nanoparticles to deliver therapeutic molecules is reported in this week’s Nature – full paper (subscription required), editors summary. See also this press release. The team, led by Mark Davis from Caltech, used polymer nanoparticles to deliver small interfering RNA (siRNA) molecules into tumour cells in humans, with the aim of preventing the growth of these tumours.

I wrote in more detail about siRNA back in 2005 here. If one can introduce the appropriate siRNA molecules into a cell, they can selectively turn off the expression of any gene in that cell’s genome, potentially giving us a new class of powerful drugs which would be an absolutely specific treatment both for viral diseases and cancers. When I last wrote about this subject, it was clear that the problem of delivering of these small strands of RNA to their target cells was going to be a major barrier to fulfilling the promise of this very exciting new technology. In this paper, we see that substantial progress has been made towards overcoming this barrier. In this study the RNA was incorporated in self-assembled polymer nanoparticles, the surfaces of which were decorated with groups that selectively bind to proteins that are found on the surfaces of the tumour cells being targeted.

The experiments were carried out as part of a phase 1 clinical trial on humans. What the Nature paper shows is that the nanoparticles do indeed accumulate at tumour cells and are incorporated within them (see the micrograph below), and that the siRNA does suppress the synthesis of the particular protein at which it is aimed, a protein which is necessary for the growth of the tumour. If this trial doesn’t demonstrate unacceptable harmful effects, further clinical trials will be needed to demonstrate whether the therapy works clinically to arrest the growth of these tumours.

Targeted nanoparticles carrying therapeutic siRNA molecules entering a tumor cell - Caltech/Swaroop Mishra

Targeted nanoparticles carrying therapeutic siRNA molecules entering a tumor cell - Caltech/Swaroop Mishra

Supporting science is about intergenerational justice

Monday, April 12th, 2010

Science and technology have not yet played a big part in the current UK general election campaign, and, to be realistic, they are probably not going to. This is despite some energetic and successful ongoing efforts to raise the profile of science in UK politics, chronicled in The Science Vote – a blog from the Campaign for Science and Engineering. The immediate problem is that the lack of discussion of science reflects a broader failure of the election debate to engage with any of the really big issues facing the country at the moment. This means that it hasn’t yet been possible to find a wider context in which to place a serious discussion of science policy. One very obvious context for that discussion is the debate we need to have about how to put our economy on a more sustainable footing. But there’s a more general way of framing the role of public support for science in terms of intergenerational justice – the legacy that each generation leaves to its successors.

One British politician who does have something of a reputation for being a deep thinker, particularly in the area of social policy, is David Willetts, currently the Conservative spokesman on Higher Education. He’s recently published a book called The Pinch – how the baby boomers stole their childrens’ future – and how they can give it back. As its title suggests, this is about intergenerational justice – the obligations we have to our children and their contemporaries. Willetts’s thesis is that the great bulge of people born between 1945 and 1965 have rigged society for their own benefit, enjoying a level of comfort and prosperity that our children will only be able to envy. Inflated house prices have priced today’s young people out of the property market, they have to pay increasing sums of money for the university education their parents received for free, and they face a future of higher taxes to pay for the pensions and healthcare of their feckless elders.

One can argue about the economic details of this thesis, as is done in this critical review by Tim Congdon, and it’s worth noting as well that there are many people in this generation who have not benefitted from this prosperity. But there’s no doubt that the argument does capture a widespread feeling – by no means restricted to the conservative end of the political spectrum – that in recent years we’ve been living off capital, whether that’s measured by the recent growth of public and private debt, or by the increasing recognition of the environmental costs of our existing economic system.

What the baby-boomers indisputably did “pinch” from their children is the prosperity that came from the last fifty years of an economy based on cheap but unsustainable fossil-fuel-based energy. But there is another side of the balance sheet. Much of our prosperity and well-being now largely depends on the science that was done in the 1950′s, 1960′s and 1970′s – for example the semiconductor physics that led to the information technology revolution, and the cell biology that permitted many developments in modern medicine. That science and technology brought its own problems, too, and we need to learn those lessons. But if people in 2050′s and 2060′s are going to be able to live more prosperous and secure lives and solve the energy and environmental problems we are leaving them, it’s largely going be because of the science we are doing now. We owe it to them to make sure we support that science.