Traditional drugs are made of small molecules that bind to and modify the function of a specific protein in the body, or in other words turn the protein’s expression “on” or “off.” Typically, the small molecules are directed to specific organs in the body that are relevant to the disease they are treating.
Where traditional drugs work by turning the function of a protein on or off, gene regulation technologies attack disease at the source. They work by preventing or correcting the production of the problematic protein from its genetic instructions.
While gene regulation technologies are helping researchers develop a better way to deliver drugs, there can still be many challenges with delivery. For example, if the drug interacts with proteins other than their targets, that can lead to complications such as unintended side effects, inefficiency of treatment, toxicity, and increased costs. Unfortunately, these challenges currently limit gene regulation drug development to a few diseases.
However, a new Northeastern spin-out company, pacDNA Inc., aims to change the status quo by developing and licensing a safe and efficient oligonucleotide delivery technology that addresses non-liver organs, reduces cost, and minimizes off-target effects.
Under the leadership of Northeastern Professor Ke Zhang, the pacDNA team is working on a drug delivery technology that solves the problem of kidney clearance, immunogenicity, and delivery to the muscle and heart. This work has earned them selection as one of the Spring 2023 Spark Fund awardees.
A new age of gene regulation therapeutics
The team at pacDNA is using the drug delivery technology to develop novel medicines for cancer and rare genetic diseases, such as Duchenne Muscular Dystrophy (DMD). The company combines short strands of nucleic acids called oligonucleotides with a proprietary oligonucleotide enhancer technology termed the Brushield™.
The Brushield™ platform can rapidly generate potent clinical leads. The technology enhances the potency of the oligonucleotides, reduces their side effects, and expands the opportunity to treat additional places in the body where an effective therapy can be developed.
“DMD has long been an industry focus given the relatively high incidence rate among rare diseases,” says Zhang. “We were immediately interested in pursuing DMD when we realized our technology could be a great fit for treating muscle diseases.”
With this work, Zhang’s laboratory is transforming the field of gene regulation therapeutics. In some preclinical models, Brushield™ reduces the dosage requirement by two orders of magnitude while suppressing side effects and immunogenicity. Furthermore, this technology solves the problem of kidney clearance, immunogenicity, and delivery to the muscle and heart.
Commercialization with the Spark Fund
Commercialization allows Zhang’s team to pursue further preclinical evaluation for DMD and other diseases. They plan to obtain proof-of-concept data on DMD to attract venture capital and support subsequent full preclinical evaluation. The team has a plan to get to a first-in-human study in three years, and ideally, new drug application in five to six years.
“Our experience applying for the Spark fund was educational,” says Zhang. “The thinking in academia and industry can be quite different from each other, so the feedback from our first application helped us craft a new, stronger proposal that was better suited for industry. Securing the Spark Fund to support our work was crucial to starting the commercialization and expansion process.”
In addition to the Spark Fund award, the team has also received other early accolades, including a $2.4M Fast-Track Small Business Technology Transfer (STTR) award. The team also received an Invented Here award from the Boston Patent Law Association for their foundational patent and a Golden Ticket award sponsored by BioMarin Pharmaceuticals, which allows them to utilize the LabCentral facilities at no charge for one year. Furthermore, the team has been selected to participate in the MassBioDrive accelerator program. All of these awards will help the team advance their work through the commercialization process.
Learn more about Zhang’s research and the five other 2023 Spring Spark Award grantees here.