What is Big Think?  

We are Big Idea Hunters…

We live in a time of information abundance, which far too many of us see as information overload. With the sum total of human knowledge, past and present, at our fingertips, we’re faced with a crisis of attention: which ideas should we engage with, and why? Big Think is an evolving roadmap to the best thinking on the planet — the ideas that can help you think flexibly and act decisively in a multivariate world.

A word about Big Ideas and Themes — The architecture of Big Think

Big ideas are lenses for envisioning the future. Every article and video on bigthink.com and on our learning platforms is based on an emerging “big idea” that is significant, widely relevant, and actionable. We’re sifting the noise for the questions and insights that have the power to change all of our lives, for decades to come. For example, reverse-engineering is a big idea in that the concept is increasingly useful across multiple disciplines, from education to nanotechnology.

Themes are the seven broad umbrellas under which we organize the hundreds of big ideas that populate Big Think. They include New World Order, Earth and Beyond, 21st Century Living, Going Mental, Extreme Biology, Power and Influence, and Inventing the Future.

Big Think Features:

12,000+ Expert Videos

1

Browse videos featuring experts across a wide range of disciplines, from personal health to business leadership to neuroscience.

Watch videos

World Renowned Bloggers

2

Big Think’s contributors offer expert analysis of the big ideas behind the news.

Go to blogs

Big Think Edge

3

Big Think’s Edge learning platform for career mentorship and professional development provides engaging and actionable courses delivered by the people who are shaping our future.

Find out more
Close
With rendition switcher

Transcript

Question: What are the potential applications of your RNAi studies in the field of cancer research?

Gregory Hannon: Well, for a long time, we’ve been interested in using RNAi as a tool to silence genes of interest, whatever genes we want.  And in fact, my lab has built large collections of RNAi inducing agents, in fact, collections that can be used to turn off every gene in the human **** genome.  Now, the way that we use these to investigate cancer biology is essentially to take a set of cancer cells, engineer them so that each cell has a different gene turned off, and then we ask how those cells react under stress.  What genes do cancer cells require that normal cells don’t?   These are potential targets for therapy.  What genes modify the responsive cancer cells to chemotherapeutic agents, or targeted therapies?  What genes modify the ability of cancer cells to engrafted host to metastasize, etc.?

Question: What new cancer therapies might be drawn from this research?

Gregory Hannon: Well there are really two ways that one would move from the work that we’re doing to something that would be applicable in the clinic.  One is a process that is being repeated in many pharmaceutical companies.  Many labs really built on the foundation of understanding this basic piece of biology, which is searching for unique vulnerabilities in tumor cells.  Now, once one finds a cell upon which a particular subtype of breast cancer, for example, depends that the normal epithelial cells don’t depend on, then one can find targeted agents using standard pharmaceutical chemistry that could inhibit the activity of that particular target.  And there you have a potentially selective therapy in a way that things like Gleevec are selective for specific gene rearrangement upon with the tumor cells carrying that arrangement uniquely depend.

Another promise of RNAi is that it can be used as a therapy itself.  And there is a tremendous interest in this, both in the academic and in the industrial communities.  The notion that pharmaceutical chemistry can only access only about 20% of the genes encoded in the genome being as we have a limited ability to regulate chemically, the activity of the proteins encoded by the other 80%.  RNAI doesn’t have such a limitation.  All it needs to be able to do is to specifically recognize the sequence of that gene in order to shut it off.  And so it is essentially, in some ways, a potentially universal pharmaceutical approach.  The difficulty is, and I think this is where many of us are focusing a lot of effort, is trying to figure out how to take this relatively large molecule compared to a normal pharmaceutical and get it efficiently delivered to the cells in which the therapy needs to operate.

And so really, that is one of the major barriers to taking this basic science discovery and really exploiting it as a tool for improving human health.

Question: How do you foresee this molecular delivery barrier being overcome?

Gregory Hannon: Well, I think that the way this barrier to delivery will be overcome is chemistry.  So, it’s clear that we’ve pushed the biology of RNAI as a silencing tool sufficiently far that, given an inability to deliver this, we could shut off any gene that we wanted to and in fact, we could probably dial the activity of these inhibitors to the point that we could even figure out exactly how far down we have to turn a gene.  Maybe you don’t want to shut it off because maybe it’s essential.  Maybe you want to inhibit its activity 50% or 80%, and the tools **** in the biology is sufficient that we can achieve that with the tools that we have. 

I think we will see advances in delivery come from is in changing the chemistry of the small RNA itself sufficiently that it can pass through cell membranes without the aid of a specific delivery agent.  Delivery agents are the other arm of research into RNAI delivery encapsulating RNAs and lipids and polymers, and that’s another strategy for getting small RNAs into cells. 

But my own feeling is that the unformulated molecules probably have the best potential to be a future therapy, the simpler formulation in something where you’re mixing an RNA agent and a series, for example, of polymers, to try to get them across the cell.

Recorded on February 9, 2010

Interviewed by Austin Allen

 

New Cancer Solutions, From ...

Newsletter: Share: