Expanded Access Case Report Shows SNIPR001, an Engineered CRISPR Phage Therapy, Associated with 89% Reduction in Multidrug-Resistant E. coli Malakoplakia Mass
核心洞察
A kidney transplant recipient with progressive, multidrug-resistant E. coli malakoplakia (搜索) received SNIPR001 via intravenous, topical, and intralesional routes under an FDA emergency IND, with no phage-related adverse events reported.
The intra-abdominal malakoplakia (搜索) mass decreased from 745 cm³ at baseline to 82 cm³ at one year, an 89% reduction, and follow-up urine and tissue cultures were negative following treatment.
SNIPR001 is a CRISPR-armed phage therapeutic designed to selectively target E. coli; it is currently in Phase 1b/2a development for preventing bloodstream infections in hematological cancer patients and holds FDA Fast Track designation.
A peer-reviewed expanded access case report published in Clinical Infectious Diseases describes the use of SNIPR001, an engineered CRISPR medicine, in a kidney transplant recipient with progressive, multidrug-resistant Escherichia coli (搜索) malakoplakia (搜索)—a rare inflammatory disease characterized by intracellular bacterial persistence within macrophages. The case, conducted by infectious disease investigators at the University of California San Diego under a single-patient emergency investigational new drug (eIND) application, marks the first clinical report of SNIPR001 administered beyond the gut.
The patient, a 65-year-old man who developed recurrent E. coli infections following a kidney transplant in 2023, had experienced disease progression despite multiple antibiotic regimens. The infecting bacterium acquired further resistance over time, eventually becoming carbapenem-resistant. Repeated biopsies continued to grow E. coli, and surgery was considered prohibitively risky due to the mass's location near the transplanted kidney and graft vasculature.
Treatment Approach and Clinical Response
SNIPR001 was administered intravenously, topically, and via intralesional injection in addition to standard-of-care therapy, including tigecycline, meropenem, fosfomycin, and other adjunctive treatments. According to the published report, treatment was associated with rapid healing of abdominal skin lesions within one week and sustained radiographic regression of disease burden.
The intra-abdominal malakoplakia (搜索) mass decreased from 745 cm³ at baseline to 82 cm³ at one year, representing an 89% reduction. The most rapid reduction occurred during the period when phage therapy was part of the regimen, with the mass shrinking by approximately half after eight weeks. Follow-up urine and tissue cultures were negative following treatment, and no phage-related adverse events were reported during SNIPR001 administration.
"This case highlights the potential of phage therapy as a precision treatment for antibiotic resistant intra-cellular infections and MDR infections in general. For a patient facing a rare infection with very limited therapeutic options, phage therapy offered a novel approach that was both well tolerated and associated with a remarkable clinical response," said Saima Aslam, MD, MS, FAST, Professor of Medicine in the Division of Infectious Diseases and Global Public Health, University of California San Diego and corresponding author on the published report.
Causality Considerations and Limitations
The improvement cannot be disentangled from the antibiotics and other treatments given alongside SNIPR001. Some antibacterial therapy continued for a year, and the clinical response could reflect SNIPR001, antibiotics, interactions between the two, or other components of care.
"Ultimately only a randomised controlled trial can partition the effect between engineered phage and the other treatments – nothing short of that settles attribution," Eric van der Helm, VP Business Development at SNIPR (搜索), told CRISPR Medicine News. "We've been deliberate about not claiming otherwise in the paper."
The investigators also did not measure how much viable SNIPR001 reached the circulation or abdominal mass after intravenous dosing, nor did they demonstrate that the phages entered macrophages to kill intracellular bacteria. Reduced extracellular bacterial burden, biofilm disruption, and phage–antibiotic synergy remain alternative explanations. Later cultures being negative—while clinically desirable—left no post-treatment isolates to analyze for phage susceptibility and resistance.
SNIPR001: Mechanism and Clinical Development
SNIPR001 combines four bacteriophages engineered with CRISPR-Cas3 (搜索) systems programmed to attack essential E. coli DNA. The phages infect susceptible bacteria and deliver the antibacterial CRISPR machinery into the bacterial cell. Preclinical work published in Nature Biotechnology in 2023 demonstrated activity against multidrug-resistant strains and selective reduction of E. coli while largely sparing other tested bacterial species.
A Phase 1a trial (NCT05277350), published in The Lancet Microbe, showed that oral SNIPR001 was well tolerated in healthy volunteers, with target engagement against intestinal E. coli and no significant differences in overall gut microbiome composition between SNIPR001 and placebo. Notably, orally administered SNIPR001 essentially remains in the gastrointestinal tract rather than distributing meaningfully into the circulation or urine—an advantage for precision gut targeting but a limitation for tissue or bloodstream infections.
SNIPR001 is currently being developed for the prevention of E. coli bloodstream infections in patients with hematological malignancies. A Phase 1b/2a trial (NCT06938867), for which recruitment is complete, is a randomized, double-blind, placebo-controlled study investigating safety, tolerability, pharmacokinetics, and pharmacodynamics of orally administered SNIPR001 in 24 patients with hematological cancer across eight US centers. SNIPR001 has received Fast Track designation from the FDA for prophylaxis of bloodstream E. coli infections in patients with hematological malignancy at risk of neutropenia.
Implications for Future Development
"This case report marks an important clinical milestone for SNIPR001 and highlights the potential of our engineered CRISPR medicine platform to address difficult-to-treat, drug-resistant E. coli infections," said Dr. Christian Grøndahl, CEO and co-founder of SNIPR (搜索). "We are grateful to the investigators at UC San Diego and to the patient and care team involved in this compassionate-use case, which provides valuable clinical insight into the potential role of SNIPR001 beyond prevention of bloodstream infections."
The expanded-access case supports investigating non-oral delivery for infections outside the gut, such as those in tissue or the bloodstream. SNIPR (搜索) says measuring active phage at the infection site would be a priority in a prospective protocol, as would banking bacterial isolates at fixed time points to monitor phage susceptibility and resistance.
Possible future treatment indications include urinary tract infections, sepsis, and infections in transplant recipients, though each would require a dedicated clinical program establishing efficacy, dosing, and delivery. For now, SNIPR (搜索)'s immediate development priority remains prevention, with the company regarding expanded access as a humanitarian route rather than an alternative to formal clinical development.
The study was performed by Saima Aslam and colleagues at the University of California San Diego and SNIPR (搜索), Copenhagen, and was published in Clinical Infectious Diseases on August 11, 2026.