Blog | March 3, 2021

In Vivo Gene Therapies, Vector Innovation, & oRNA — Oh My!

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By Anna Rose Welch, Editorial & Community Director, Advancing RNA

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There is so much C&G-related company news coming out these days, from partnerships and CMO/supplier agreements to regulatory submissions, facility constructions, and/or clinical milestones. This will be FAR from an all-inclusive list. For those of you interested in an exhaustive list of weekly news, I’d direct you the “Sector Vector” newsletters ARM sends out weekly. (I desperately wish I had come up with that name.)

In the meantime, here were a few headlines that caught my eyes in recent weeks showcasing some of the “off-the-beaten path” (or upcoming trends) being explored in the C&G spaces.

  • Ensoma: This spinoff of Fred Hutchinson Cancer Research Center and University of Washington is working on an in-vivo gene therapy boasting a “gutless” engineered adenoviral vector. This vector, which the company termed “Engenious,” is devoid of its viral DNA or RNA, which eliminates immunogenicity risks and increases genetic payload capacity (as much as 3-times current generation vector capacity). The company believes it can target a broad array of diseases outside the rare disease space, and that the therapy can be given as a single injection at a typical outpatient facility without preconditioning or apheresis at a specialized treatment center. A great profile of the company and its long-term goals can be found here.
  • Nkarta: This allogenic NK-cell therapy company claims to have “mastered cryopreservation.” (A bold claim!) Cryopreservation has been a major pain point for many in this industry — in fact, some have even gone so far as to emphasize their desire to eliminate this step entirely from the cell therapy development process. For NK-cells especially, cryopreservation can lead to changes in their structure and function. Observe, this study in Nature Communications on cryopreservation’s impact on NK-cell cytotoxicity. See also this study in Advanced Science suggesting alternative approaches to the commonly used cryoprotectant dimethyl sulfoxide, which is ill-equipped for NK-cells.
  • Generation Bio: Three key words/phrases to note here right off the bat: non-viral, redosable, and COGS of a biologic. The company — which, FYI, is still in preclinical studies — is working with close-ended DNA and lipid nanoparticles to overcome the packaging challenges inherent with AAV and LV vectors. Their early-stage technology promises a packaging capacity of 12 kilobases to permit delivery of larger genes or multiple genes. They’re also working on capsid-free manufacturing in the hopes it will be more easily scalable — in line with that of a standard biologic.
  • Novartis & Gates Foundation: Over the past five years, Novartis has been surveying the gene therapy landscape to determine the most promising future technologies. They’ve landed on an in-vivo gene therapy for sickle-cell disease that can be delivered with a single injection in any country — even less developed nations. The Bill & Melinda Gates Foundation has provided the funds to help Novartis on its mission, and the Gates are willing to give more to other firms interested in tackling gene therapy development for low-resource nations.
  • Orna Therapeutics: In the wake of the mRNA buzz, this new startup is digging into engineered circular RNA — or oRNA. This oRNA promises a longer half-life than mRNA and better protein-coding potential compared to circRNA. The oRNA would be delivered into the body (i.e., the liver) using lipid nanoparticles. However, there are also aspirations to carry out in-vivo CAR treatments by transporting CAR directly to immune cells in the body.