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Start-ups

Radar Therapeutics launches for targeted treatments

RNA sensor technology switches on protein production only in specific cells

by Laura Howes
May 24, 2024

 

A team of seven smiling people. Two are seated on office chairs in front of the other five.
Credit: Radar Therapeutics
Sophia Lugo (seated, left) with the Radar Therapeutics team

“What CRISPR is to DNA, ADAR is to RNA.” That’s how Sophia Lugo, CEO of the new biotechnology firm Radar Therapeutics, describes the endogenous RNA editor that the company is trying to co-opt to produce therapeutic proteins in specific cells. The firm has launched with $13.4 million in seed funding.

ADAR stands for “adenosine deaminase acting on RNA.” It is essentially a protein in our cells that sweeps in when our RNA becomes double stranded. This protective enzyme makes a small edit in the double-stranded RNA so the body recognizes it as its own rather than coming from dangerous outside sources like viruses.

Radar is now using that editing system and combining it with messenger RNA (mRNA) technology to treat diseases.

The company’s name comes from the technology behind its platform, RNA sensing using ADAR. Radar licensed the technology from Stanford University, where it was developed by chemical engineer Xiaojing Gao and his team and first reported in October 2022 (Nat. Biotechnol., DOI: 10.1038/s41587-022-01493-x). The same month, other institutions published similar RNA sensors based on ADAR (Nature, DOI: 10.1038/s41586-022-05280-1; Nat. Biotechnol., DOI: 10.1038/s41587-022-01534-5).

In all three studies, the researchers designed RNA strands encoding a stop sign, called a stop codon, and a protein. When the synthetic RNA bound to its target, ADAR would swoop in, edit the stop sign to turn it off, and so trigger the body to produce the encoded protein.

Radar has refined the technology further with the help of cofounder and synthetic biology expert Jim Collins of the Massachusetts Institute of Technology. The newer Radar probes are modular and include a section encoding a therapeutic protein, a binding module that can specifically bind to target RNA, and a small loop containing the stop codon. According to Lugo, that loop can be fine-tuned to optimize the ADAR editing and the expression of the therapeutic protein.

Lugo says the RNA can be encapsulated in different delivery vectors, including the lipid nanoparticles that are used in mRNA-based COVID-19 vaccines. But unlike with those vaccines, protein expression is turned on only in cells with target RNA that corresponds to a disease state or specific cell type.

Lugo won’t say precisely which therapeutic areas the small team of seven full-time employees will focus on first. But she says they see the technology as being broadly applicable, including delivering cytotoxic drugs to cancer cells and delivering ligands and antibodies to “undruggable” proteins.

“We find our design space is really broad,” she says.

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