NIPT Market Disruption: Bohao Gene's Global-First Tri-Integrated Non-Invasive Prenatal Screening Product Passes Registration Inspection
A Policy Puts Single-Gene Disorder Testing in the Spotlight of Non-Invasive Prenatal Screening
On December 14, 2021, the “Notice of the General Office of the State Council on Issuing the National Action Plan for Disability Prevention (2021–2025)” explicitly stated that prenatal screening should be widely implemented, and prenatal screening and diagnosis for major birth defects—such as common fetal chromosomal abnormalities, severe fetal structural malformations, and monogenic genetic disorders—should be strengthened.Affirmed the importance and urgency of monogenic disease testing in the non-invasive prenatal screening market.
Historically, non-invasive prenatal screening (NIPS) has been predominantly associated with non-invasive prenatal testing (NIPT). Both NIPT and NIPT Plus are limited to the detection of chromosomal abnormalities, including aneuploidies and microdeletions/microduplications. Chromosomal abnormalities account for 10% of birth defects.
In fact, monogenic disorders account for a significant proportion of birth defects. Monogenic disorders include autosomal dominant, autosomal recessive, and X-linked monogenic disorders, with a combined incidence rate of 1%. There are over 8,000 known types of these disorders, the majority of which lack effective treatments. Among individuals with birth defects, monogenic disorders account for 7.5%–14%, with domestic data indicating that this proportion can be as high as 22.2%.
Unlike NIPT, non-invasive prenatal screening for monogenic diseases is still in its early stages due to extremely high technical barriers. While policy attention and clinical demand are rising rapidly, few companies have entered this field, making itThe New Blue Ocean in the Non-Invasive Prenatal Screening Market Following NIPT.
Bohao Genetics is one of the few companies in China to have established a presence in non-invasive prenatal screening (NIPS) for monogenic disorders.Bohao Genomics’ flagship product for detecting dominant monogenic disorders, “Haoyuntian,” has already been implemented in hospitals. The company is also developing a “three-in-one” solution that covers monogenic disorder testing, chromosomal aneuploidy, and chromosomal microdeletions/microduplications. This “three-in-one” product has passed registration testing and represents the world’s first of its kind. As a result, Bohao Genomics has garnered interest from multiple top-tier venture capital firms and has previously completed four rounds of financing totaling hundreds of millions of yuan.
The founding team of Bohao Genomics has many years of experience in the field of non-invasive prenatal screening (NIPT). Dr. Zhang Zhiwei, Founder and President, possesses profound expertise in both NIPT and newborn monogenic disease screening products.
Dr. Zhang Zhiwei told VCBeat, “NIPT emerged in 2011 and experienced rapid market growth after 2014. However, the NIPT sector has been marked by significant homogenization of technical products. In 2016, I predicted that NIPT would soon face price wars, prompting me to seek new opportunities.” The current development trajectory of NIPT aligns closely with Dr. Zhang’s earlier predictions.
Drawing on his experience with genetic screening products for hereditary deafness, Dr. Zhang Zhiwei is highly optimistic about the application of monogenic disease testing in the field of non-invasive prenatal screening (NIPS). “If cell-free fetal DNA from maternal peripheral blood could be used to screen for monogenic diseases prenatally, the resulting clinical value would be immeasurable.” This insight inspired Dr. Zhang to develop a prenatal screening technology for monogenic diseases and to integrate the detection of chromosomal abnormalities and monogenic disorders into a unified platform.
However, prenatal screening for monogenic disorders is technically highly challenging, and integrating the detection of chromosomal abnormalities with that of monogenic disorders is even more difficult.
First, the technical threshold for monogenic disease detection is exceptionally high. The non-invasive prenatal testing (NIPT) products currently marketed in China employ low-coverage whole-genome sequencing. Monogenic diseases typically involve mutations at a single or a few nucleotide bases, generally requiring a sequencing depth of over 1000x, with a minimum lower limit of 200x. Low-coverage whole-genome sequencing fails to meet these requirements and is therefore unsuitable for monogenic disease detection. Since coding regions constitute only 2% of the entire genome sequence, using high-coverage whole-genome sequencing for monogenic disease detection would incur prohibitively high costs, yield a low cost-effectiveness ratio, and entail prolonged data analysis times. Consequently, its overall performance cannot meet the requirements for prenatal screening, rendering it clinically impractical.
Furthermore, from the perspectives of reducing reagent costs, minimizing instrument and equipment requirements, saving operational time, and optimizing staffing, it is necessary to integrate monogenic disease testing with chromosomal abnormality detection to enable simultaneous screening for both conditions from a single blood sample. However, the previously employed technical workflows for detecting monogenic diseases and chromosomal abnormalities are incompatible, posing significant technical challenges.
Therefore,Although domestic and international manufacturers have launched non-invasive prenatal screening products for monogenic diseases, there remains a gap in the market for integrated testing capable of detecting both monogenic diseases and chromosomal abnormalities.
Dr. Zhang Jinglan, Co-founder and Chief Scientist of Bohao Genetics, previously led a team at a major U.S. medical center to develop various single-gene disorder testing technologies for large-scale populations, such as NGS-based screening for spinal muscular atrophy, carrier screening for hundreds of autosomal recessive monogenic disorders, and non-invasive prenatal screening for multiple autosomal dominant monogenic diseases.
Among them, Dr. Jinglan Zhang, Dr. Jianli Li, and others at Baylor College of MedicinePioneering Non-Invasive Prenatal Testing for Multiple Monogenic Disorders (30 Genes, 44 Conditions), with the findings published in Nature Medicine, generating significant impact within the industry. Dr. Zhang Jinglan believes that,Non-invasive prenatal screening for monogenic diseases requires further technological innovations to enhance detection performance, and should be integrated with traditional chromosomal disorder screening to improve the efficiency of population-based screening.thereby further promoting its widespread adoption. This concept aligns precisely with Dr. Zhang Zhiwei’s vision for the future development of next-generation NIPT.
Driven by a shared vision to advance non-invasive prenatal screening (NIPS) technologies and benefit more families, Dr. Zhang Zhiwei and colleagues founded BoHao Genomics (Beijing Bohao Yuntian Technology Co., Ltd.). In early 2019, Dr. Zhang Jinglan joined BoHao Genomics, and together they have been dedicated to addressing the challenges of non-invasive prenatal testing for monogenic disorders and integrated detection of monogenic disorders and chromosomal abnormalities.
For monogenic disease testing, Bohao Gene adoptsProbe-Based Targeted Capture High-Depth Sequencing Technology, first capture the target regions using probes, then perform high-depth sequencing, which enables accurate detection of point mutations while effectively controlling costs,It addresses the limitations of insufficient sequencing depth in low-coverage whole-genome sequencing and the prohibitive costs associated with high-coverage whole-genome sequencing.
Among monogenic disorders, autosomal dominant conditions account for approximately 53%. However, most monogenic autosomal dominant disorders causing severe birth defects arise from de novo mutations. Primary prevention (preconception screening) is ineffective, and tertiary prevention (newborn disease screening) is too late; thus, the prenatal period represents the only critical window for intervention to prevent transmission.“Hao Yun Tian” Non-Invasive Prenatal Testing Product for Dominant Monogenic Disorders“Haoyuntian” is Bohao Gene’s flagship product, which has been implemented in multiple hospitals since its launch.Tests all exons, splice sites, and key intronic regions across 64 genes, covering approximately 300,000 loci, enabling accurate detection of 92 autosomal dominant monogenic disorders with a combined incidence of 1/400.
In the integration of monogenic diseases and chromosomal abnormalities, Bohao GeneticsSuccessful application of collaborative allele-targeted capture high-depth sequencing technology for chromosomal abnormality detection,Resolved the incompatibility issue between detection technologies for chromosomal abnormalities and monogenic disorders. Currently, it covers “detection of chromosomal aneuploidy, chromosomal microdeletions/microduplications, and monogenic disorders.”The “three-in-one” product and its accompanying software have passed registration testing.A retrospective clinical study of over a thousand specimens has shown that itsSensitivity: 100%; Specificity: 99.7%. Furthermore, the multicenter prospective clinical study of the “three-in-one” product, launched in June last year and led by the Obstetrics and Gynecology Hospital of Fudan University, is nearing completion of patient enrollment, follow-up, and study closure.
Bohao Genetics holds full independent intellectual property rights to this technology, with its core patents approved by the China National Intellectual Property Administration.“Over the past three years, we have achieved significant original innovations in key reagents centered on hybridization probes, wet-lab workflows, and bioinformatics algorithms. The technical development challenges exceeded our expectations, but we ultimately overcame numerous obstacles to complete product development. This technology represents a major breakthrough in the field of non-invasive prenatal screening,” said Dr. Zhang Zhiwei.
Dr. Zhang Zhiwei noted: “Leading prenatal diagnostic centers have demonstrated exceptionally high recognition and acceptance of non-invasive prenatal screening (NIPS) for monogenic disorders, with the market on the verge of explosive growth.“Next, Bohao Genomics will leverage provincial-level prenatal diagnosis centers as an entry point to rapidly implement non-invasive prenatal screening for monogenic disorders across prenatal diagnosis centers at all levels. Within the year, Bohao Genomics will also launch a ‘three-in-one’ product that integrates non-invasive prenatal testing for chromosomal aneuploidies, chromosomal microdeletions and microduplications, and monogenic disorders. ‘After holding online departmental meetings with dozens of hospitals, we found that the vast majority of directors of prenatal diagnosis centers are highly anticipating this,’ said Dr. Zhang Zhiwei.”
The Ideal State of Non-Invasive Prenatal Screening Is“One blood draw, one test, to screen for as many fetal genetic disorders as possible”Next, Bohao Genomics will expand the disease coverage of its dominant monogenic disorder testing technologies and pilot non-invasive whole-exome sequencing, while accelerating the clinical trials and regulatory registration of its “three-in-one” product. Simultaneously, the company will initiate product upgrades and iterations, launching R&D efforts for additional offerings such as non-invasive prenatal testing for recessive monogenic disorders. By centering on the field of non-invasive prenatal screening, Bohao Genomics aims to build the most comprehensive solution portfolio and reshape the market landscape with its proprietary technologies.