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October 14, 2010

RNA-induction: A new method for iPS cell production

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Hi Paul,
Good points. I alluded to them in the OP, thanks for expanding - and I hope I didn't imply this tech was going to the clinic right away.

The use of viruses or protein attachments (eg. HIV-Tat) immediately sprung to mind when considering possible delivery, though both may be an odd choice for this particular system. The paper is quite explicit that a significant benefit of the modified mRNAs is avoiding the use of viruses and inefficiencies of proteins for transduction. Viral envelopes may avoid integration issues but still raise issues of immune response. You're right that delivery is a bottleneck, though I doubt it will be long before we start seeing papers optimizing delivery of these modified mRNAs.

What is exciting about the Rossi paper is the way they modify normal protein coding RNAs to help the molecules evade destruction in normal cells.

You leave off on the idea of delivering CFTR to a Cystic Fibrosis patient with these RNAs, which is a great example of an application for RNAs (i.e. supplementing a mutated or deleted gene). However, this kind of technology will still restricted to the lab for the near future as delivery of RNAs in a clinical context is something that still challenges the RNA biotech industry.

A few technologies that can help to target and deliver RNA payloads (i.e. siRNAs, shRNAs, mRNAs) to a particular location, such as packaging in viral envelopes that infect the target cells or generating RNAs attached to protein or RNA based antibodies that recognize a cell specific receptor. Except for a few examples where RNAs can be delivered directly, such as the respiratory system, specific and effective delivery technologies are the missing link in making of effective RNA drugs.

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