AskBio’s Jude Samulski Seeks Patent for Gene-editing System

 

Jude Samulski, Ph.D. -- AskBio photo
Jude Samulski, Ph.D. -- AskBio photo

Jude Samulski, Ph.D., a pioneer in using small viruses to insert therapeutic genes into cells, has been awarded an international patent application by the World Intellectual Property Organization for his regulated gene-editing system.

The system applies the advantages of the new gene-editing tool known as CRISPR while limiting the tool’s disadvantages.

“We started investigating this technology about 10 years ago, before CRISPR came along,” Samulski said in a news release. The system was developed as part of a toolkit to control adeno-associated virus (AAV) vectors used in gene therapeutics, he said.

AAVs are small viruses that can infect cells without causing any known harm, making them ideal vectors, or carriers, of genetic material into cells.

“Working at the intersection of gene editing and AAV, my team and I found that this regulated gene-editing system, used in vivo (in living cells), is more precise and has higher specificity and reliability for its target,” Samulski said.

Patent would be latest of many

Samulski’s patent application is a Patent Cooperation Treaty (PCT) filing that has not yet been prosecuted to determine which portions will be allowed or rejected. By filing one application under the PCT, applicants can simultaneously seek patent protection for an invention in many countries.

Samulski holds the first U.S. patent for inserting non-AAV genes into AAV, and he is the lead inventor on more than 300 patents in the field of AAV vectors and gene therapy.

He was recruited to the University of North Carolina School of Medicine in 1993 with nearly $250,000 in grant funding from the North Carolina Biotechnology Center. He has led UNC’s Gene Therapy Center for several years and co-founded Asklepios BioPharmaceutical (AskBio), a clinical stage AAV gene therapy company, in 2001.

AskBio, based in Research Triangle Park, is dedicated to developing life-saving medicines that cure genetic disease. Its pipeline includes clinical-stage programs in Pompe disease and congestive heart failure and a preclinical portfolio of therapeutics targeting neuromuscular, central nervous system and other diseases, as well as out-licensed clinical indications for hemophilia and Duchenne muscular dystrophy. 

AskBio has spun out four gene therapy startups in recent years: NanoCor Therapeutics, Chatham Therapeutics, Bamboo Therapeutics and Actus Therapeutics. Chatham was acquired by Takeda, and Bamboo was acquired by Pfizer.

In May 2019 AskBio raised $225 million in equity funding and another $10 million from founders and board members. The funding was the largest single round of venture capital financing ever for a North Carolina bioscience company.

“The impact of Jude Samulski’s continuing commitment to develop ever-more effective AAV-based gene therapies will be life-changing to patients afflicted with genetic-based disorders,” said Rob Lindberg, Ph.D., vice president of science and technology development at the Biotech Center. “We’re excited that this gene editing approach directly addresses significant challenges that hamper current gene therapies.”

Since 1993, NCBiotech has invested nearly $1.5 million in grants and loans to recruit Samulski to UNC, support his gene therapy research and launch several of his startup companies, including AskBio.  Those investments have enabled an additional $373 million in subsequent funding brought into North Carolina, equating to a $250 return on each $1 invested by the Center.  

“This is a powerful statement that speaks to the benefits that can be realized through sustained and patient investment in high-caliber life sciences research,” Lindberg said.

Advantages of Samulski’s gene-editing system

One of the challenges of using CRISPR for gene editing is off-target effects.

Proteins involved in CRISPR act like molecular scissors to cut targeted genes, and CRISPR does not stop making the active proteins without some type of on/off switch. This can lead to unintended genetic mutations, or off-target effects. In addition, the proteins involved are derived from bacteria, which raises the risk of provoking an immune response, or immunogenicity.

Samulski’s regulated gene-editing system uses an oligonucleotide -- a short DNA or RNA molecule -- that can regulate the function of any gene by selectively turning on or off the expression of the gene. The oligonucleotide can be used to regulate the CRISPR proteins, reducing their potential for off-target effects.

This regulation system is independent of any promoter, so various promoters can be used to target specific tissues and cells, enabling the treatment of a large number of genetic diseases.

Oligonucleotides, which are FDA approved to treat a number of diseases, are better than other gene-control approaches that use drugs, which can cause side effects and greater risk of toxicity. The oligonucleotide on/off switch shows promise in both single-gene diseases and in multi-gene disorders such as congestive heart disease.

The gene-editing system also addresses redosing concerns. The potential for gene therapy redosing and future treatment options is diminished if a person has developed an immune response to the proteins found in the therapeutic vectors. Oligonucleotides can be given repeatedly to control the gene function.

“Both the oligonucleotide and AAV technologies have regulatory approval for use in the clinical setting, so that gives me confidence that we can take advantage of the synergy to apply this system to gene therapeutics,” Samulski said. “The technology is an ideal platform to advance the science of gene editing not only at AskBio but throughout the scientific and clinical community.”

 

Barry Teater, NCBiotech Writer
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