Microdose jet injection reveals a tissue-dependent retention–expression window for carrier-free nucleic acid delivery
4 affiliations
- 1One Time Energy Collaborative Laboratory, Institute of Industrial Nanomaterials, Kumamoto University, Kumamoto, Japan
- 2Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan
- 3Research Center & Life Science SBU, Tokyo Head Office, Daicel Corporation, Tokyo, Japan
- 4Laboratory of Molecular Cellular Biology, School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan
Abstract
Efficient local nucleic acid delivery requires not only access to target cells but also retention of the administered payload. Yet whether increasing physical delivery input improves or compromises functional delivery remains poorly understood. Here, we show that microdose jet injection operates within a tissue-dependent retention–expression window that can be interpreted in terms of physical jet input. Using the Actranza Lab needle-free system, sub-microlitre to low-microlitre jet outputs were calibrated and characterised by high-speed imaging, defining a kinetic-energy range of approximately 0.38–18.5 mJ. Delivery outcomes were evaluated in mouse spleen, liver, and skin using dye-retention analysis and luciferase expression. In spleen and liver, low-volume jets were associated with local retention and high volume-normalised luciferase expression, whereas increasing jet input progressively increased retention failure and reduced expression efficiency despite larger administered DNA amounts. In contrast, skin maintained local retention over a substantially broader input range, and total luciferase expression showed a significant positive association with injection volume. At the same 1-µL splenic administration volume, Actranza Lab produced approximately 34-fold greater luciferase activity than a 30-G Hamilton microsyringe. Cross-tissue integration of retention-failure frequency and volume-normalised expression revealed narrower operational windows in spleen and liver and a broader window in skin. These findings show that successful carrier-free jet delivery is determined not by nominal dose alone, but by the interaction between physical jet input and tissue retention. This retention–expression framework provides a practical basis for tissue-specific optimisation of needle-free nucleic acid delivery.
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BibTeX
@article{terai2026microdose,
title = {{Microdose jet injection reveals a tissue-dependent retention–expression window for carrier-free nucleic acid delivery}},
author = {Kazuhiro Terai and Ryusho Kariya and Hiromi Ogata-Aoki and Hiromitsu Iga and Satoshi Sakamoto and Seiji Sakano and Seiji Okada},
journal = {Drug Delivery},
year = {2026},
month = oct,
doi = {10.1080/10717544.2026.2738976},
url = {https://doi.org/10.1080/10717544.2026.2738976},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Microdose jet injection reveals a tissue-dependent retention–expression window for carrier-free nucleic acid delivery
AU - Kazuhiro Terai
AU - Ryusho Kariya
AU - Hiromi Ogata-Aoki
AU - Hiromitsu Iga
AU - Satoshi Sakamoto
AU - Seiji Sakano
AU - Seiji Okada
PY - 2026
DA - 2026/10/30
JO - Drug Delivery
DO - 10.1080/10717544.2026.2738976
UR - https://doi.org/10.1080/10717544.2026.2738976
AB - Efficient local nucleic acid delivery requires not only access to target cells but also retention of the administered payload. Yet whether increasing physical delivery input improves or compromises functional delivery remains poorly understood. Here, we show that microdose jet injection operates within a tissue-dependent retention–expression window that can be interpreted in terms of physical jet input. Using the Actranza Lab needle-free system, sub-microlitre to low-microlitre jet outputs were calibrated and characterised by high-speed imaging, defining a kinetic-energy range of approximately 0.38–18.5 mJ. Delivery outcomes were evaluated in mouse spleen, liver, and skin using dye-retention analysis and luciferase expression. In spleen and liver, low-volume jets were associated with local retention and high volume-normalised luciferase expression, whereas increasing jet input progressively increased retention failure and reduced expression efficiency despite larger administered DNA amounts. In contrast, skin maintained local retention over a substantially broader input range, and total luciferase expression showed a significant positive association with injection volume. At the same 1-µL splenic administration volume, Actranza Lab produced approximately 34-fold greater luciferase activity than a 30-G Hamilton microsyringe. Cross-tissue integration of retention-failure frequency and volume-normalised expression revealed narrower operational windows in spleen and liver and a broader window in skin. These findings show that successful carrier-free jet delivery is determined not by nominal dose alone, but by the interaction between physical jet input and tissue retention. This retention–expression framework provides a practical basis for tissue-specific optimisation of needle-free nucleic acid delivery.
SN - 1071-7544
SN - 1521-0464
ER -