RNAi therapy involves researchers producing snippets of RNA, a close relative of DNA, that match a portion of a gene of interest. When administered, this so-called small interfering RNA (siRNA) causes the destruction of that gene’s products before it can be turned into a protein.
The specificity of RNAi for targeting particular genes has attracted a lot of interest from people who want to use it as a clinical treatment. “Today’s platforms target the protein that causes the disease and bind to that protein. We stop the protein from being made in the first place,”
…But a recurring challenge for the therapeutic RNAi field is how to deliver the siRNAs to the right place in the body. On their own, the small molecules do not survive long in the bloodstream, so simply injecting a patient with a solution of unprotected siRNAs is not effective.
“The key technical hurdle is getting the siRNA [inside] the right cells,” says Greene. For several of its projects, Alnylam uses nanoparticles to protect and deliver its siRNAs, which can then be delivered by injection.
But for genetic diseases that originate in the brain, the body’s own defenses, namely the blood-brain barrier, complicate delivery further. To circumvent the blood-brain barrier, which prevents most molecules from leaving the bloodstream and entering the brain, Alnylam has looked to a different delivery mechanism: direct dosing of unpackaged siRNAs.