Non-viral gene therapy to treat and prevent atherosclerosis

The National Heart, Lung, and Blood Institute awarded Emmune Inc. $299,664 on September 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to develop a non-viral gene therapy vector for treating and preventing atherosclerotic cardiovascular disease.

Emmune will leverage lipid nanoparticle (LNP) technology to achieve non-immunogenic gene delivery of a therapeutic protein capable of treating and preventing atherosclerosis. The company has discovered a novel approach to deposit DNA into the nucleus of long-lived non-dividing cells such as muscle when DNA is delivered to the cytoplasm by LNPs, which dramatically enhances gene transfer efficiency compared to existing viral vector approaches. Phase I will demonstrate proof-of-concept in mice. Phase II will optimize non-immunogenic gene transfer via LNPs and LNP formulation, then demonstrate that LNP vectors efficiently and non-immunogenically deliver the payload to sustain stable expression in non-human primates, facilitating development of a commercial product capable of treating and preventing atherosclerosis after a one-time treatment.

The award is structured as a fast-track Small Business Innovation Research (SBIR) grant. Performance occurs in Cambridge, Massachusetts, with an ultimate completion date of February 28, 2027.

Abstract

Adeno-associated virus (AAV) vectors can introduce a non-integrating circular DNA episome capable of persisting in the nucleus of long-lived non-dividing cell types such as muscle, but have a number of drawbacks including high manufacturing cost. Lipid nanoparticles (LNPS) offer numerous advantages over viral vectors, but are unable to efficiently deliver DNA to the nuclei of long-lived non-dividing cells capable of lifelong therapeutic gene expression. After fusing with or disrupting the endosomal membrane, LNPS deliver their contents to the cytoplasm. Whereas mrna only needs to be delivered to the cytoplasm to be expressed, DNA needs to be delivered to the nucleus. We have discovered a novel strategy to deposit DNA into the nucleus of long-lived non-dividing cell types such as muscle, when that DNA has been delivered to the cytoplasm by LNPS. This approach dramatically enhances the efficiency gene transfer by LNP vectors in muscle. The highest impact application of this technology is a non-viral gene therapy vector based on LNPS for treating and preventing atherosclerotic cardiovascular disease (ASCVD). Under this grant, we will leverage the LNP platform to achieve non-immunogenic gene delivery of a therapeutic protein capable of treating and preventing ASCVD. Under this fast-track sbir grant, we will first demonstrate proof-of-concept in mice in phase I. Under phase II, we will optimize non- immunogenic gene transfer via LNPS and LNP formulation, and then demonstrate that our LNP vectors efficiently and non-immunogenically deliver their payload to sustain its stable expression in non-human primates. These studies will facilitate the development of a commercial product capable of treating and preventing ASCVD after a one-time treatment with a non-viral gene therapy vector.