Automated Gene Synthesis for Personalized Medicines

This week, leading researchers and professionals will gather for the annual American Society of Gene and Cell Therapy meeting in Chicago. At this highly anticipated event, researchers will present research and clinical data with the latest advancements in genetic and cellular therapies. SGI-DNA is excited to participate in this prominent and influential gathering. Sr. Product Manager, Dr. Michael Sturges will present: “cGMP Synthetic Gene Synthesis to Enable Precision Medicine” (poster #320) on Wednesday, May 16 at 5:30 pm.  

Personalized medicines (or precision medicines) constituted 1 out of every 4 drugs approved by the US FDA over the past 4 years¹ and last year was no exception with 35% of FDA-approved “new molecular entities” classified as personalized medicines. Several concomitant factors have contributed to the growth of this burgeoning field, including the revolutionary improvements in genome sequencing technology, including advances in biomedical informatics and data analytics.

Human monoclonal antibody (mAb)-based targeted therapy toward various cancers constitutes a large portion of personalized medicines. Cancer immunotherapy often targets immune checkpoint proteins with the goal of increased T cell production to harness endogenous immune activity against cancer cells. One example is programmed death-ligand 1 (PD-L1), which is upregulated in certain cancers, causing a reduction in T cell activity, thereby contributing to uncontrolled tumor cell growth. Two fully human mAb therapeutics, avelumab and durvalumab, that target programmed death-ligand 1 (PD-L1), were approved last year. Bavencio (avelumab) was approved for the treatment of metastatic Merkel cell carcinoma and Imfinzi (durvalumab) was approved for the treatment of advanced urothelial carcinoma. Both of these therapeutics are considered personalized medicines since the decision to administer these agents can be based on PD-L1 expression levels in the tumors of patients.

While these medicines are considered “personalized,” these therapies are still based on predictive group outcomes. An entirely new type of personalized medicine is emerging, however, that tailors a specific treatment to an individual patient. One novel therapy includes targeting neoantigens or peptides found only on the surface of cancer cells for cancer vaccines. Although none have been approved to date, several neoantigen therapeutics are in development or early stage clinical trials. All of these neoantigen-based therapeutics rely on upstream DNA synthesis for development and production of the customized therapeutic.

As this relatively recent class of DNA-based pharmacological agents continues to emerge in research, development, and in clinical trials, the infrastructure to support these therapeutics must be established and validated. One of the biggest challenges in customized, personalized neoantigen treatment plans is the turnaround time required. In order to create a custom treatment, a patient’s DNA must be sequenced and analyzed to allow for the identification of the targeted neoantigens. Production of the customized therapeutics must then be in accordance with cGMP (current good manufacturing practice). Traditional methods can take several months, a time that is incompatible with successful intervention.

To address this need for the development and rapid production of customized, personalized medicines, SGI-DNA established a cGMP production laboratory for synthetic DNA constructs.

The addition of the BioXp 3200 System –a fully automated, genomic workstation that rapidly generates high-quality linear double-stranded DNA fragments and clones them into a vector using the Gibson Assembly^â method—will accelerate and streamline customized construct production. The qualification of the BioXp System for inclusion in the cGMP manufacturing is in progress.

To learn more about SGI-DNA instrumentation and the deployment of the cGMP suite, please visit us at the American Society of Gene and Cell Therapy Annual Meeting in Chicago, during the Oligonucleotide Therapeutics I Poster Session (#320) on Wednesday, May 16 at 5:30 pm.

References

1.        www.personalizedmedicinecoalition.org/Resources/Personalized_Medicine_at_FDA_An_Annual_Research_Report