Genome Editing

On the first day of the American Association for Cancer Research (AACR) annual meeting, the synthetic biology company Synlogic presented data from a Phase I trial of their immunotherapy drug, SYNB1891. The drug, which consists of engineered bacteria that are injected intratumorally, is being developed for the treatment of solid tumors and lymphoma. The data suggest that the drug is safe, well-tolerated, and activates the STING pathway in patients.

Scientists led by a team at the Whitehead Institute developed a gene editing technology, CRISPRoff, that utilizes a programmable, epigenetic memory writer protein to silence gene expression, without altering the underlying DNA sequence. Studies showed this epigenetic memory is heritable for hundreds of cell divisions, is fully reversible, and can also be used to silence non-coding genome elements such as enhancers.

The synthetic biology revolution is here! In this presentation, sponsored by Twist Bioscience, we are excited to bring together leaders in the field. Our April episode of GEN Live, our guests discuss where the field is now and the exciting advances in store for the future.

Challenges facing phage therapy range from a developing regulatory landscape and the design of clinical trials to the up-scaling of manufacturing processes. With lots of good science, practicality considerations, and clinical strategies along with funding concerns, the 3rd Bacteriophage Therapy Summit provided a great opportunity to discuss the current state of phage therapy and the pathway to regulatory approval.

A Penn Medicine patient with a genetic form of childhood blindness gained vision, which lasted more than a year, after receiving a single injection of an experimental RNA therapy into the eye. Results from the Scheie Eye Institute in the Perelman School of Medicine at the University of Pennsylvania trial showed that the treatment led to marked changes at the fovea, the most important locus of human central vision. The treatment was designed for patients diagnosed with Leber congenital amaurosis (LCA), an eye disorder that primarily affects the retina, who have a CEP290 mutation.

Producing a safe and effective AAV-based treatment is not easy: The steps taken to extract and purify AAV vectors are not perfect. And ultimately, an imperfect product can put patients at risk. Many of the quality issues associated with AAV development stem from the fact that AAVs are produced in live cells in cell culture. GEN dives into the top five bioprocessing challenges that AAV developers face.

Although the industry still relies on transient transfection, due to the difficulty of creating stable production cell lines, a shift from adherent to suspension culture is underway.

Manufacturers are developing new analytical tools to satisfy increasingly stringent regulatory requirements.

Developers of gene therapies are taking advantage of new vector technologies, incorporating CRISPR systems, and augmenting gene therapy with targeted therapies and immunotherapies.

Rather than inject loose collections of therapeutic cells, implant 3D-bioprinted tissue constructs and gain more control over cell-based precision medicine applications.