Altamira Therapeutics

Extrahepatic delivery
of therapeutic nucleic acids

The OligoPhore™ / SemaPhore™ platform

Altamira Therapeutics is developing OligoPhore™ / SemaPhore™ as a versatile platform for safe and effective delivery of nucleic acid payloads such as siRNA (small interfering ribonucleic acid), mRNA (messenger ribonucleic acid) into target cells, using systemic or local administration.

  • siRNA is one type of oligonucleotide which can be used therapeutically to silence disease-related genes in a specific manner.

  • mRNA can be used therapeutically to translate genetic code from DNA into proteins, which then can be used to replace abnormal or deficient proteins or make proteins to fight or prevent disease.

The Greek word “phore” means an agent or bearer or producer of a specified thing. OligoPhore™ allows for carrying oligonucleotides such as siRNA into cells. The Greek word “sema” means a signal or message. SemaPhore™ allows for carrying messenger RNA into cells.

Current challenges with nucleic acid delivery

There exist various carriers for delivering nucleic acids into cells, such as viral-based vectors, lipid nanoparticles (LNPs), and ligand conjugates. Although each of these system exhibits promising features, robust nucleic acid delivery remains the key rate-limiting step for unlocking the full potential of RNA therapeutics. For example, LNPs and currently available ligand conjugates using GalNac technology preferentially target the liver, which essentially precludes their use for targeting non-liver tissues.

How OligoPhore™ / SemaPhore™ work

OligoPhore™ / SemaPhore™ are based on a proprietary 21 amino acid peptide that rapidly condenses peptide and nucleotide components into a polyplex. The polyplex has a size, charge, and other physical features that allow it to escape hepatic clearance and thus to reach other target tissues than the liver. It readily escapes the leaky vasculature of various pathologies, and is taken up avidly by cells that are capable of macropinocytosis (“cell drinking”), such as cancer cells or macrophages. However, OligoPhore™ / SemaPhore™ polyplexes have also been shown to transfect endothelium, smooth muscle, and other cell types. Once in the endosome, the natural process of acidification breaks strong bonds between the RNA and the peptide to disassemble the polyplex. The released peptide interacts with the endosomal membrane to permeabilize it and release the RNA into the cytoplasm. The peptide is then diluted quickly and broken down, and has been designed to cause no unintential damage to the targeted cell.

Current status of the technology

Our OligoPhore™ / SemaPhore™ technology has been tested in numerous standard murine models, both with siRNA and mRNA payloads. Several key features of the nanoparticles have emerged from these studies:  

High stability
RNA complexed in nanoparticle format remains stable in the blood circulation and is only released inside of cells after uptake

Extrahepatic delivery
The nanoparticles are not sequestered in the liver, but reach other tissues 

Efficient endosomal escape
pH-dependent nanoparticle disassembly, followed by full release of RNA into the cytoplasm

High selectivity
The nanoparticles can be administered systemically, but target only diseased tissues

No cellular or adaptive immune responsivity to nanoparticle components or RNA after multiple serial doses and no organ toxicities have been observed


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