AAV Gene Therapy Pioneer Jude Samulski Develops Proprietary Regulated Gene Editing System

Technology brings together benefits of AAV and CRISPR while minimizing negative effects that occur during gene editing

Research Triangle Park, N.C. – June 23, 2020 – Asklepios BioPharmaceutical, Inc. (AskBio), a leading, clinical-stage adeno-associated virus (AAV) gene therapy company, today announced that Jude Samulski, PhD, President, Chief Scientific Officer and Co-founder, has been awarded an international patent application from the World Intellectual Property Organization (WO/2020/076892) for his regulated gene editing system. This system applies the advantages of gene editing while limiting genome-wide off-target effects, immunogenicity and repeat dosing challenges that can potentially occur when using CRISPR.

“We started investigating this technology about 10 years ago, before CRISPR came along, as part of our toolkit to apply control over AAV vectors used in gene therapeutics,” said Samulski. “Working at the intersection of gene editing and AAV, my team and I found that this regulated gene editing system used in vivo is more precise and has higher specificity and reliability for its target.”

One of the challenges in using CRISPR for gene editing is off-target effects. Cas9 proteins involved in CRISPR act like molecular “scissors” to cut the targeted genes, and CRISPR does not stop making the active protein without some type of on/off switch. This can lead to unintended 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 small molecule that can regulate the function of any gene by selectively turning on or off the expression of the gene. This molecule can be used to regulate the CRISPR proteins and thereby reduce their potential for off-target effects. This regulation system is independent of any promoter; therefore, various promoters can also be used in combination with the system to target specific tissues and cells in order to treat a large number of genetic diseases.

Oligonucleotides, which are FDA approved to treat a number of diseases, are superior to other gene control approaches that use a variety of drugs that carry side effects and greater risk of toxicity. The oligonucleotide on/off switch shows promise in both monogenic and complex disorders such as congestive heart disease (CHF), which arise from changes in multiple genes where genes must be expressed at certain times.

The 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, while the oligonucleotides can be administered repeatedly to control 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 continued. “The technology is an ideal platform to advance the science of gene editing not only at AskBio but throughout the scientific and clinical community.”

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

About AskBio
Founded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, fully integrated AAV gene therapy company 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 growing preclinical portfolio of therapeutics targeting neuromuscular, CNS and other diseases, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). AskBio’s gene therapy platform includes Pro10™, an industry-leading proprietary cell line manufacturing process, and an extensive AAV capsid and promoter library. With global headquarters in Research Triangle Park, North Carolina, and European headquarters in Edinburgh, UK, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. Learn more at https://www.askbio.com or follow us on LinkedIn.


Robin Fastenau
Vice President, Communications
+1 984.275.2705