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Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
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Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
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Targeted Intracellular Delivery via Precision Programming of ARRDC1-Mediated Microvesicles.

Zhi Qiao1, Sengjin Choi1, Zunwei Chen1

  • 1Departments of Environmental Health & Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Journal of Extracellular Vesicles
|December 15, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed engineered microvesicles (ARMMs) for targeted delivery of mRNA and CRISPR gene editors. This platform enables precise therapeutic macromolecule delivery to specific cell types, advancing gene and RNA-based medicine.

Keywords:
ARMMsmRNA and CRISPR therapeuticsnon‐viral deliveryprecision medicinetargeted delivery

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Area of Science:

  • Biotechnology
  • Molecular Medicine
  • Cell Biology

Background:

  • Efficient and cell-specific delivery of nucleic acids and gene editing tools like mRNA and CRISPR is crucial for therapeutic applications.
  • Current delivery methods face challenges in targeting specific cell populations, limiting therapeutic efficacy.

Purpose of the Study:

  • To develop a versatile and programmable delivery platform for targeted delivery of therapeutic macromolecules.
  • To engineer microvesicles for selective cargo delivery to defined cell types using cell-specific ligands.

Main Methods:

  • Engineered ARRDC1-mediated microvesicles (ARMMs) were decorated with Nipah virus (NiV)-derived proteins and cell-specific ligands (anti-CD8 scFv or DARPin targeting GluA4).
  • ARMMs were functionalized to target CD8+ T cells and parvalbumin-positive (PV+) neurons.
  • In vitro and in vivo studies were conducted to assess the targeted delivery efficiency and functional cargo release.

Main Results:

  • ARMMs functionalized with anti-CD8 scFv selectively delivered protein, mRNA, and CRISPR-Cas9 base editors to CD8+ T cells.
  • ARMMs displaying a DARPin targeting GluA4 enabled delivery to PV+ neurons.
  • In vivo administration demonstrated functional delivery to CD8+ splenocytes and PV+ cortical neurons in mice.

Conclusions:

  • Surface-engineered ARMMs represent a programmable and modular system for precision delivery of therapeutic macromolecules.
  • This platform has broad applicability in gene and RNA-based medicine, overcoming key delivery barriers.
  • The study establishes a novel approach for targeted delivery of mRNA and CRISPR-based therapeutics.