NIH, Biotech Partner on Electro-Aided Crispr for Sickle Cell

Sickle cell illustration (National Heart, Lung, and Blood Institute)

11 June 2018. The National Heart, Lung, and Blood Institute and a biotechnology company are testing genome editing with electronically treated cells as a therapy for sickle cell disease. The arrangement between MaxCyte Inc. in Gaithersburg, Maryland and NHLBI, part of National Institutes of Health, involves sharing of the agency’s facilities and expertise, with no direct payment of funds.

MaxCyte offers a technology called flow electroporation exposing cells to an electrical field that the company says makes the treated cells more susceptible to transfection, including the addition of nucleic acids, such as DNA or RNA. In this case, flow electroporation is used with the genome editing technique known as Crispr, short for clustered, regularly interspaced short palindromic repeats, to correct mutations in genes producing hemoglobin, responsible for sickle cell disease.

Crispr harnesses bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The actual editing is done most often by the Crispr-associated protein 9, or Cas9, enzyme that programs RNA to silence genes and provide immunity against invading genetic material.

Sickle cell disease is a genetic blood disorder affecting hemoglobin, a protein in blood that delivers oxygen to cells in the body. People with sickle cell disease have hemoglobin molecules that cause blood cells to form into an atypical crescent or sickle shape. That abnormal shape causes the blood cells to break down, lose flexibility, and accumulate in tiny capillaries, leading to anemia and periodic painful episodes. Sickle cell disease is prevalent worldwide, and affects 70,000 to 80,000 people in the U.S., including about 1 in 500 people of African descent.

The company says its flow electroporation process makes possible transfection with more than 80 different types of cells with an efficiency exceeding 90 percent. For this project, MaxCyte is providing messenger RNA, or mRNA, molecules to help develop an efficient process for delivering corrected hemoglobin genes, as well as correct mutations in non-mutated cells that may contribute to the disease. NHLBI is expected to carry out safety and effectiveness tests with MaxCyte’s mRNA molecules in preclinical models of sickle cell disease.

The deal between MaxCyte and NHLBI is called a cooperative research and development agreement, or Crada. A Crada a collaborative project where agencies or national labs make their staff, facilities, and equipment available for research with a private company that also provides funding for the project, as well as its own staff, facilities, and equipment. Crada agreements often include provisions for licensing the results of the joint research, but no intellectual property aspects of this agreement were disclosed.

This is the second such agreement between an NIH institute and MaxCyte. As reported in Science & Enterprise in January 2017, MaxCyte and National Institute of Allergy and Infectious Diseases collaborated on using flow electroporation with Crispr-Cas9 to repair a genetic blood disorder known as X-linked chronic granulomatous disease, an inherited condition where phagocytes, white blood cells in the immune system, do not produce the proteins that protect against invading pathogens, such as bacteria and fungi.

More from Science & Enterprise:

• FDA Delays Crispr Trial for Inherited Blood Diseases
• Long-Term Effects Shown from Hemophilia Gene Therapy
• Genetic Repair Company Starts-Up, Gains $87 Million
• Crispr Deployed to Correct Inherited Vision Disorder
• Cellectis, Wyss Inst. Partner on Recoding Human Genome

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