Delivery Platforms

Our RNA interference (RNAi) therapeutics utilize two distinct approaches to enable delivery of small interfering RNA (siRNA) to target tissues—lipid nanoparticles (LNPs) and conjugates. We are continually improving and expanding our novel delivery systems and applying them to new organs and diseases.

Our RNAi therapeutics utilize specially designed siRNA to seek out and disable messenger RNA (mRNA) involved in the cause or “pathway” of diseases, therefore “interfering” with gene transcription. But for these siRNA to reach the target mRNA, they must be precisely and efficiently delivered to the tissue where the mRNA are converted to proteins. Alnylam scientists have pioneered the use of LNPs and conjugates for drug delivery.

Learn more about the science of RNAi therapeutics.

Lipid Nanoparticles (LNPs)

Lipid nanoparticles (LNPs) are chemically synthesized multicomponent lipid formulations (~100 nm in size) encapsulating siRNAs for delivery to the target tissue. En route to their destination, the siRNAs encapsulated in LNPs are protected against degradation by ubiquitous nucleases. The LNPs used by Alnylam preferentially distribute to the liver because of their affinity for apolipoprotein E (apoE), an endogenous ligand for the low-density lipoprotein receptor (LDLR) expressed on the surface of liver cells (hepatocytes).

RNAi therapeutics utilizing LNP technology are administered intravenously (IV). Our first approved RNAi therapeutic, ONPATTRO® (patisiran), utilizes LNP-based delivery.

We are proud to see that our pioneering work in the use of LNPs for drug delivery has been utilized by several of our biopharmaceutical peers for the development of vaccines for COVID-19, the disease caused by SARS-CoV-2.

Conjugates

Conjugates are defined single chemical entities with fully modified siRNA conjugated to targeting ligand to help them find their way to a specific cell or tissue within the body. Conjugates are a “lock and key” system, where the lock is the receptor found on the target cell and the key is the ligand attached to the siRNA.

We leverage two conjugate approaches to enable targeted delivery to the liver and the central nervous system (CNS)—GalNAc conjugates and CNS-targeted siRNA conjugates.

GalNAc conjugates – GalNAc, or N-acetylgalactosamine, is a sugar molecule that can recognize and bind to a cell surface protein, the asialoglycoprotein receptor (ASGPR), which is abundantly expressed on liver cells (hepatocytes). The binding affinity to the receptor increases exponentially if several GalNAc units are combined into a multivalent ligand. Our GalNAc-conjugated siRNAs are trivalent, meaning that three GalNAc molecules are clustered and conjugated to one siRNA molecule. This setup guarantees high affinity (strength) of the interaction between ASGPR and the GalNAc ligand, thus promoting optimal efficiency of siRNA delivery to the liver.

RNAi therapeutics utilizing GalNAc conjugate technology are administered subcutaneously. Our medicines GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran)* utilize GalNAc conjugate delivery.

CNS/Ocular-targeted siRNA conjugates – Our preclinical pipeline features several intrathecally administered siRNA conjugates engineered for delivery to the central nervous system (CNS) and the eye.

 

*Licensed to Novartis

OUR PIPELINE

Learn about how we are leading the translation of RNAi (RNA interference) into a whole new class of innovative medicines.

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OUR PRODUCTS

Learn more about our FDA-approved therapies.

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