Bionano Announces Publication Demonstrating Utility of OGM to Assess Genome Integrity of CRISPR-Edited Cells as Part of Gene Therapy Development

Rhea-AI Summary

Bionano Genomics, Inc. (Nasdaq: BNGO) announced a study demonstrating the use of optical genome mapping (OGM) to identify structural variations introduced by CRISPR-Cas9 gene editing of CD4+ T-cells, revealing the potential limitations of such edited cells for therapeutic use. The study found that while ddPCR assays are suitable to characterize certain expected mutations, they may miss large SVs. OGM outperformed karyotyping's resolution and sensitivity, revealing unexpected gene editing events and off-target structural variations. The study highlights the importance of comprehensive genome analysis in developing gene therapies.

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• Potential limitations of CRISPR-Cas9 edited cells for therapeutic use
• 20-50% of the edited cells expressing the rescued gene did not undergo precise editing
• Detection of 11 nonrecurring SVs outside of the target locus
• Risks of on-target and off-target structural variations during CRISPR-Cas9 genome editing

SAN DIEGO, Nov. 29, 2023 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) today announced a publication demonstrating the use of optical genome mapping (OGM) to identify structural variations (SVs) introduced by CRISPR-Cas9 gene editing of CD4+ T-cells that could potentially limit the therapeutic use of such edited cells.

The research study authors used OGM in combination with drop-off digital PCR (ddPCR) to assess genome integrity of cells that were edited by CRISPR to restore gene function in Hyper IgM1 (HIGM1), an X-linked combined immunodeficiency caused by CD40LG mutations which can lead to liver disease, cancer and infections. The study authors describe that while ddPCR assays are suitable to characterize certain expected mutations, they may miss large SVs that are either outside the regions targeted by ddPCR primers or are too big to be detected by ddPCR.

The study authors first validated OGM’s performance at high coverage to capture unexpected gene editing events and found that it outperformed karyotyping’s resolution and sensitivity. OGM then revealed the presence of concameters missed by the ddPCR assay, indicating that 20-50% of the edited cells expressing the rescued gene did not undergo precise editing. In addition, OGM detected 11 nonrecurring SVs outside of the target locus, demonstrating its genome-wide ability to detect off-target events. The study authors concluded that using OGM early in the development of the gene therapy could enable researchers to reduce the number of ddPCR assays needed in the final product quality control panel.

“This study highlights how researchers can use OGM when developing cell and gene therapies. The expansion of gene therapy faces risks due to both on-target and off-target structural variations that may be introduced during CRISPR-Cas9 genome editing. Since genome aberrations caused by CRISPR-Cas9 editing could lead to unforeseen adverse effects, we believe careful and comprehensive analysis of edited genomes is important for quality control while developing these therapies and their manufacture," commented Erik Holmlin, PhD, president and chief executive officer of Bionano.

The paper is available at: https://www.embopress.org/doi/full/10.15252/embj.2023114188.

About Bionano

Bionano is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Company’s mission is to transform the way the world sees the genome through OGM solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen, Inc. d/b/a Bionano Laboratories business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. The Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants and absence of heterozygosity across the genome in one consolidated view. The Company additionally offers nucleic acid extraction and purification solutions using proprietary isotachophoresis technology. For more information, visit www.bionano.com, www.bionanolaboratories.com or www.purigenbio.com. 

Unless specifically noted otherwise, Bionano’s OGM products are for research use only and not for use in diagnostic procedures.

Forward-Looking Statements of Bionano Genomics

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “believe,” “can,” “could,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the potential utility of OGM in identifying on-target and off-target structural variations introduced by CRISPR-Cas9 gene editing; the utility and ability of OGM to be used as part of developing cell and gene therapies and the manufacture thereof; the importance of comprehensive analysis of edited genomes in order to develop cell and gene therapies and their manufacture; and our ability to drive adoption of OGM and our technology solutions to be used as part of developing cell and gene therapies and the manufacture thereof. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the timing and amount of revenue we are able to recognize in a given fiscal period; the impact of adverse geopolitical and macroeconomic events, such as recent and potential future bank failures, global pandemics and the ongoing conflicts between Ukraine and Russia and Israel and Hamas, on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive technologies or improvements to existing technologies; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts and our ability to continue as a “going concern”; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; study results that differ or contradict the results mentioned in this press release; failure of OGM to prove useful in uncovering SVs in CRISPR-Cas9 edited genomes; failure of OGM to be used as part of developing cell and gene therapies and their manufacture; failure of and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2022 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTS
Company Contact:
Erik Holmlin, CEO
Bionano Genomics, Inc.
+1 (858) 888-7610
eholmlin@bionano.com

Investor Relations:
David Holmes
Gilmartin Group
+1 (858) 888-7625
IR@bionano.com

FAQ

What did Bionano Genomics, Inc. (BNGO) announce?

Bionano Genomics, Inc. (Nasdaq: BNGO) announced a study demonstrating the use of optical genome mapping (OGM) to identify structural variations introduced by CRISPR-Cas9 gene editing of CD4+ T-cells.

What are the potential limitations of CRISPR-Cas9 edited cells for therapeutic use?

The study found that 20-50% of the edited cells expressing the rescued gene did not undergo precise editing, and OGM detected 11 nonrecurring SVs outside of the target locus, demonstrating the risks of on-target and off-target structural variations during CRISPR-Cas9 genome editing.

What did the study authors use OGM in combination with?

The study authors used OGM in combination with drop-off digital PCR (ddPCR) to assess genome integrity of cells that were edited by CRISPR to restore gene function in Hyper IgM1 (HIGM1), an X-linked combined immunodeficiency caused by CD40LG mutations.

What did the study conclude regarding the use of OGM in the development of gene therapy?

The study concluded that using OGM early in the development of the gene therapy could enable researchers to reduce the number of ddPCR assays needed in the final product quality control panel.

Who commented on the importance of comprehensive genome analysis in developing gene therapies?

Erik Holmlin, PhD, president and chief executive officer of Bionano, commented on the importance of comprehensive genome analysis in developing gene therapies.