One of the major challenges in the clinic for the treatment of various diseases is the ability to consistently deliver therapeutics at efficacious levels. Recently, researchers in the Division of Hematology and Oncology at Nationwide Children’s Hospital engineered a single dose of gene therapy using adeno-associated virus (AAV) to safely express a therapeutic protein in the bloodstream, which resulted in tumor regression and demonstrated its efficacy as a treatment for lymphoma.

Bispecific antibodies and CAR T cells have recently gained popularity as therapeutics for treating hematological malignancies; however, their use in the clinic has been hindered by challenges with delivery and manufacturing. Dr. Timothy Cripe and his team were able to design secreted bispecific antibodies targeting cancer and immune cells delivered by a single dose of AAV that were expressed at sustained levels for up to a year. This proof of principle study demonstrated that their engineered genetic therapy is effective in treating a humanized-mouse model of lymphoma without adverse toxicity.

Further, Dr. Cripe and the team at Nationwide Children’s Hospital were able to optimize their gene therapy design by modifying their AAV serotype, engineering their promoter, and by adding a post-transcriptional regulatory element. In addition, the team developed an inducible version of their construct that was also able to target KRAS, a gene frequently mutated in cancers. Overall, this study demonstrated the potential efficacy of a single dose of gene therapy in treating cancer.

Construction of AAV and vectors was enabled by VectorBuilder’s online Vector Design Studio. VectorBuilder offers custom and pre-made AAV vectors that can be packaged into a variety of serotypes for your gene delivery needs—click here to learn more. Contact us to find out more or use our award-winning online platform to design and order custom vectors specific to your research needs.

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Source (https://www.science.org/doi/10.1126/sciadv.abm1890)

Cripe TP, Hutzen B, Currier MA, Chen CY, Glaspell AM, Sullivan GC, Hurley JM, Deighen MR, Venkataramany AS, Mo X, Stanek JR, Miller AR, Wijeratne S, Magrini VJ, Mardis ER, Mendell JR, Chandler DS, Wang PY. Leveraging Gene Therapy to Achieve Long-Term Continuous or Controllable Expression of Biotherapeutics. Science Advances. 2022 Jul 13.