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Uricase-Expressing Engineered Macrophages Alleviate Murine Hyperuricemia.

Yu-Zhong Feng1, Hao Cheng1, Guo-Qing Xiong1

  • 1Academy of Military Medical Sciences, Beijing 100071, China.

Biomedicines
|November 27, 2024
PubMed
Summary

Engineered macrophages expressing uricase offer a safe and effective method to lower uric acid levels in hyperuricemia (HUA) models. This approach avoids the immunogenicity issues associated with direct uricase injections, presenting a promising alternative treatment strategy.

Keywords:
engineered macrophageshyperuricemiamacrophage therapyuricase

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Area of Science:

  • Biochemistry
  • Immunology
  • Cell Biology

Background:

  • Uricase (urate oxidase) is crucial for uric acid metabolism and treating hyperuricemia.
  • Current uricase therapies face immunogenicity challenges, leading to adverse effects and reduced efficacy.
  • Engineered macrophages expressing uricase present a novel therapeutic alternative.

Purpose of the Study:

  • To develop and evaluate engineered macrophages as a delivery system for uricase to treat hyperuricemia.
  • To assess the safety and efficacy of uricase-expressing macrophages in a hyperuricemic mouse model.

Main Methods:

  • RAW264.7 cells were engineered to stably express uricase.
  • Engineered macrophages were intravenously injected into hyperuricemic KM mice.
  • Serum uric acid, liver/kidney function markers, and inflammatory cytokines were analyzed; histological examination was performed.

Main Results:

  • Uricase-expressing macrophages reduced uric acid levels by 66.2% in vitro.
  • In vivo, engineered macrophages normalized serum uric acid levels in HUA mice by day 14 (48.6% decrease).
  • The treatment demonstrated safety, with no observed liver/kidney dysfunction or systemic immune response, and efficacy comparable to allopurinol.

Conclusions:

  • Macrophages serve as a viable chassis for uricase delivery.
  • This engineered cell-based therapy offers a safe and effective strategy for hyperuricemia management.
  • This approach overcomes the immunogenicity limitations of traditional uricase treatments.