In-utero gene therapy nears its first FDA trial: Tippi MacKenzie's pioneering work
Dr Tippi MacKenzie, professor of fetal surgery at the University of California, San Francisco (UCSF), is a pioneer in the scientific field of 'in-utero gene therapy'. According to the latest detailed report from STAT News, MacKenzie's team has reached the stage of having a clinical trial for type A hemophilia approved by the US Food and Drug Administration (FDA). This could be the first gene therapy applied at the fetal stage in world history.
Type A hemophilia is an inherited bleeding disorder caused by a deficiency in the Factor VIII protein the body needs to stop bleeding. It occurs in roughly 1 in 5,000 male births and is much rarer in female infants. In severe untreated patients, joint bleeds, intracranial bleeds and complications that seriously limit quality of life develop. The standard treatment is the administration of Factor VIII injections weekly or every two weeks; the modern protocol is effective but lifelong.
The approach MacKenzie proposes is the transfer of a functional copy of the underlying F8 gene to the fetus via an injection delivered under ultrasound guidance between gestational weeks 20-26. The aim is for the F8 gene, packaged in a genetic vector (AAV -- adeno-associated virus), to reach the fetus's liver cells and produce Factor VIII from there. A single injection holds the potential to deliver a treatment that lasts the child's whole life.
The study's earlier preclinical phases were conducted on sheep and monkeys. According to STAT, in primate (monkey) studies, the single injection delivered to the fetus sustained Factor VIII production into the adult life period after birth (in animals followed for three years). Side effects detected in animals -- transient elevation in liver enzymes, small delays in fetal development -- were measured at controllable levels; but the preclinical data had to reach safety standards sufficient for a human trial.
For the FDA filing, MacKenzie's team prepared a 220-page dossier over the past three years. The dossier also includes the safety record of fetal surgery procedures (operations performed on a baby in the womb) that have been carried out since the 1980s; the more than 800 cases performed by MacKenzie's team over the past 25 years demonstrate the procedure's basic safety for mother and baby. FDA 'fast track' approval was expected within the past six weeks.
The first phase of the clinical trial will cover 12 participants -- male fetuses diagnosed with type A hemophilia in utero. Diagnosis is made via prenatal genetic screening; the family must give written consent to participate in the gene therapy trial. Ethics committee approval was granted by the UCSF Institutional Review Board in March 2026. The child will be followed annually after birth for Factor VIII levels and clinical bleeding signs.
The ethical dimension of the study is important. In-utero gene therapy is a therapy directed at an existing disease; it does not constitute 'germline' (reproductive cell) modification. The gene settles only in the fetus's liver cells; even though these cells are chromosomally modified, the change is not passed on to the person's future children. There is therefore no connection between this therapy and a 'CRISPR babies' debate within international medical ethics rules. MacKenzie said in an interview with STAT, 'this therapy changes only the health of one person; not the future of the human species.'
On the financial side, the clinical trial is funded by an NIH (National Institutes of Health) federal grant; in addition $25 million of private-sector investment is supported (by a BioMarin Pharmaceutical and Sangamo Therapeutics partnership). BioMarin retains the right to commercialise should a successful treatment protocol emerge; with the average cost of Factor VIII hemophilia treatment in the United States running between $250,000 and $700,000 annually, a one-time in-utero gene therapy could create major economic savings.
There is also international competition. Alongside the United States, Great Ormond Street Hospital in the United Kingdom and the Beijing Pediatric Research Institute in China are conducting parallel in-utero gene therapy studies. The British team has filed in parallel to the MHRA on a track alongside the FDA application; the Chinese team is using a different AAV vector and is at an earlier research phase. Which country gains the first clinical approval will be an important data point in the global competition of the gene-therapy field.
Should in-utero gene therapy be successfully approved, application could become widespread for other inherited diseases within the next 10 years: cystic fibrosis, Tay-Sachs disease, sickle cell anemia. Expectations in the scientific community for this approach are high but cautious -- preclinical data are promising, but long-term safety in human trials has not yet been established. This article is for science news and does not substitute for individual medical advice. Families with a hemophilia or other genetic-disease diagnosis should consult specialist doctors about treatment decisions.