RNAi drug company promises delivery – of both results and RNA

ORIGINAL: OBR Review

by Stefano Iantorno

January 9, 2013

RNA interference may be a widely used technique in molecular biology, but adapting this biological process to the development of RNAi-based drugs has posed a vexing problem for scientists since its discovery in 1998, which earned Craig Mello and Andrew Fire the Nobel Prize in 2006. A recent advancement by UCSD professor Steven Dowdy shows promise in allowing the short nucleic acids composing RNA and microRNA molecules to cross cell membranes, and in this way blocking the activity of genes involved in cancer and other diseases.

UCSD School of Medicine. biomedsci.ucsd.edu. 

The technology, which is protected intellectual property of the University of California San Diego and revolves around “masking” the negative charge of double-stranded RNA molecules with specific side groups which are then later clipped off by a naturally occurring enzyme, has been licensed in an exclusive deal to the three-month old, half-dozen-employees spin-out company Solstice Biologics LLC. The company was founded by Prof. Dowdy along with Chief Scientific Officer Curt Bradshaw, former vice president of chemistry at CovX Pharmaceutical, a company which was acquired by Pfizer in 2007. Prof. Dowdy was also the scientific founder of Traversa Therapeutics, which filed for bankruptcy in April last year.

Previous companies that have invested copiously in attempting to solve this problem with no robust results include pharmaceutical giants such as Merck, Alnylam, and Roche. Professor Steven Dowdy and colleagues may however be nearing a solution with their cell-permeable RNAi pro-drug, which they called RiboNucleic Neutrals (RNNs). Other companies, such as Merck, have favoured an approach using antisense nucleic acid analogues such as morpholinos, which mimic single stranded nucleic acids and are able to cross the cell membrane in a neutral or slightly positively charged state. Unlike small interfering RNA, morpholinos do not degrade their target RNA molecules, but instead bind to complementary sequences and prevent binding of other interacting partners via steric blocking.

The company has announced in a January 4th press release a partnership with San Francisco-based VenBio and Aeris Capital AG in the form of a $18 million USD series A commitment to the San Diego start-up to achieve a set of pre-established “milestones and goals” over the next 18 months, said VenBio’s Dr. Corey Goodman, who also sits on Solstice’s board as executive chairman. While it is unclear at this early stage whether the technology will actually work in humans and animals, the potential therapeutic benefits are great, and can be applied to a wide range of diseases.

Dr. Goodman, previously a tenured professor at Stanford University and at University of California Berkeley and head of Pfizer’s Biotherapeutics and Bioinnovation Center, further explained that this early stage financing will allow further development of the technology platform and testing to ensure that the process “works and is safe for humans”. He anticipates the company to license the RNN technology to drug developers, once at least one working therapeutic has been taken into early clinical trials. In case the RNAi drug will fail to provide the expected results, he envisaged that the underlying technology could be sold to a reagent company for developing research lab chemicals. The global market for RNAi drug delivery was worth $7 billion USD in 2010, and is expected to grow to nearly $24.1 billion by 2015 according to a January 2011 report by BCC Research.