MaxCyte has launched two sequencing-based assays to identify potential off-target sites for adenine and cytosine base editing therapies.

New assays target base editing safety

The CHANGE-seq-BE and ONE-seq-BE assays are available through MaxCyte’s SeQure service and are designed to support off-target assessment for adenine base editors (ABEs) and cytosine base editors (CBEs).

Off-target activity is an important safety consideration in genome editing because an editor can alter DNA at sites other than its intended target. Identifying potential off-target sites allows developers to select sites for further confirmation and quantitative assessment.

CHANGE-seq-BE is a biochemical method designed to nominate potential off-target sites without relying on a specific cell type, while ONE-seq-BE incorporates information on genetic variants that could affect off-target activity in different populations.

The assays can be used alongside MaxCyte’s existing SeQure confirmation services, which include quantitative assessment of off-target editing and detection of structural variation.

Maher Masoud, president and CEO of MaxCyte, said: “Base editors are creating new opportunities for therapeutic development, while also requiring safety assessment strategies that reflect their mechanisms of action.”

Genetic variation adds another safety consideration

Human genetic variation can affect the potential location and activity of genome editing off-target sites.

FDA’s draft guidance on safety assessment of genome editing in human gene therapy products recommends that developers consider genetic variation when analysing potential off-target sites. The guidance notes that genetic variants can create or alter potential sites for off-target editing and recommends approaches that account for variation in relevant populations.

This makes population-specific analysis particularly relevant as genome editing therapies progress through development.

ONE-seq-BE is designed to provide visibility into population-specific genetic variants that may affect off-target activity, according to MaxCyte.

The company said combining different off-target nomination approaches can help developers identify overlapping and distinct potential sites before selecting regions for confirmation testing.

Supporting genome editing development

The launch expands MaxCyte’s SeQure offering for developers working with genome editing therapies.

The company said the two new assays provide complementary approaches to off-target site nomination, which can then be followed by confirmation assays to quantify editing at selected sites and assess structural variation.

The assays are intended for use during therapeutic development, where off-target data can contribute to the safety assessment of genome editing candidates and support regulatory submissions.

Masoud added that the new assays are intended to help developers better understand off-target risk and build data packages for clinical development.

The launch comes as regulatory expectations around genome editing safety continue to develop, with FDA’s draft guidance placing emphasis on appropriate off-target assessment, assay sensitivity and consideration of the specific genome editing modality.