Gene therapy companies look beyond adeno-associated viruses

Gene therapy has largely relied on adeno-associated viruses (AAVs) as vessels to carry and deliver new genes to replace defective or missing ones in people with gene-related conditions. AAVs are small, single-stranded DNA viruses of the parvovirus family. Both gene therapies that are approved by the US Food and Drug Administration, Zolgensma and Luxturna, use them, but several new companies are looking to alternative approaches to overcome what they say are shortcomings of AAVs as gene delivery vectors.

The latest one to launch, Carbon BioSciences, has received $38 million in series A financing for its non-AAV parvovirus gene therapy platform. The parvoviruses it’s using have several advantages over AAVs, CEO Joel Schneider says.

“For the last three decades, there’s been a major focus on these adeno-associated viruses, because it’s made sense, because we found ways to package genes in them, and we found ways to manufacture and move them into the clinic,” Schneider says. “But there’s absolutely no reason why we can’t go larger, and look at the larger field of parvoviruses.”

Carbon’s parvoviruses effectively target specific tissues, Schneider says. They also bring about minimal neutralizing immunity within the body, meaning that the same gene therapy can be readministered after the initial dose and not be fought off by the body’s immune system. And they are 30–40% larger than AAVs, enabling larger payloads.

These benefits come in handy for Carbon’s lead candidate, CGT-001, for cystic fibrosis, a condition that leads to lung damage and makes breathing difficult. Existing data show it can deliver the full-length CFTR gene that is mutated in people with cystic fibrosis, it can be readministered, and it targets lung tissue, Schneider says. CGT-001 is in the proof of concept stage, he says.

Several other companies have debuted in recent months with non-AAV gene therapy technologies. Kelonia Therapeutics, which launched with $50 million in series A financing in April, uses lentiviral vector-like particles to deliver genetic payloads. It aims to develop gene therapies for a range of diseases. “We’re able to generate highly potent, highly concentrated lentiviral delivery tools that separate us from other gene therapy approaches,” says Kevin Friedman, Kelonia’s chief scientific officer.

Code Biotherapeutics, which announced $75 million in series A financing early in June, has stepped away from viral delivery altogether, and is using a multivalent synthetic DNA delivery platform, called 3DNA, that relies on companion targeting molecules, according to the company. After the targeting molecules bind to surface proteins on target cells, the 3DNA is taken into the cell and delivers its genetic payload. Code’s two lead programs are geared toward treating Duchenne muscular dystrophy and type 1 diabetes.