2024-12-18 コロンビア大学
コロンビア大学の耳鼻咽喉科医アニル・ラルワニ博士と機械工学者ジェフリー・カイザー博士のチームは、従来の針よりもはるかに細く鋭い3Dプリント製のマイクロニードルを開発しました。このデバイスは、内耳の蝸牛内にある直径約2mmの膜を損傷することなく貫通し、遺伝子治療などの精密な治療法を直接投与することを可能にします。これにより、騒音曝露などで失われた聴覚細胞の再生を促進し、聴力回復の新たな手段となることが期待されています。研究者たちは、このマイクロニードルが内耳の精密医療において重要な役割を果たすと確信しています。この研究は、2024年12月18日にコロンビア大学アービング医療センターのニュースで発表されました。
<関連情報>
- https://www.cuimc.columbia.edu/news/most-interesting-needle-world#
- https://www.academicradiology.org/article/S1076-6332(24)00783-9/abstract
- https://journals.lww.com/otology-neurotology/abstract/2024/10000/microneedle_mediated_delivery_of_sirna_via.22.aspx
円窓膜を介したガドジアミドの直接マイクロニードル蝸牛内注入による蝸牛の造影増強と最小限の投与量 Contrast Enhancement of Cochlea after Direct Microneedle Intracochlear Injection of Gadodiamide through the Round Window Membrane with Minimal Dosage
Chaoqun Zhou, MS∙ Sharon J. Feng, MD∙ Stephen Leong, MD∙ … ∙ Jia Guo, PhD, Assistant Professor of Neurobiology∙ Jeffrey W. Kysar, PhD∙ Anil K. Lalwani, MD…
Academic Radiology Published:November 4, 2024
DOI:https://doi.org/10.1016/j.acra.2024.10.022
Abstract
Rationale and Objectives
The potential of contrast-enhanced MRI for diagnosing endolymphatic hydrops is limited by long wait times following intravenous (IV) or intratympanic (IT) delivery, high contrast dosages, and inconsistent signal intensity enhancements. This study investigates microneedle-mediated intracochlear (IC) gadodiamide injection for consistent and efficient contrast delivery with minimal contrast dosage.
Materials and Methods
A 100 µm diameter microneedle with 35 µm lumen was used to inject 1 µL of diluted gadodiamide (17.4 mM) into a guinea pig cochlea via the round window membrane. Serial MRI imaging was performed in a post-mortem animal using a 9.4 T small-animal MRI. Maximum intensity projections of MRI scans were generated to visualize diffusion of contrast within cochlea over time; mean intensities in defined regions of interest (ROIs) were calculated. Contrast diffusion time and intensity enhancements were determined.
Results
Contrast was observed in the basal turn of scala tympani (ST) and scala vestibuli (SV) in the first MRI scan for all subjects which was acquired as early as 35 min after injection. Two-tailed paired t-tests confirmed that contrast reached the first two turns of ST and SV within 60 min, and the second half of third turns and apical turns of ST and SV within 90 min (p < 0.05). Intensity enhancements, defined as the percentage increase of the ROI mean intensity in the injection side compared to the contralateral side, exceeded 100% in the first turn and ranged from 12% to 32% in the third and apical turns of ST and SV at 90 min after injection.
Conclusions
IC gadodiamide enables controllable and efficient contrast delivery with significantly lower contrast dosage, making it a viable alternative for contrast-enhanced cochlear MRI.
内耳遺伝子治療のためのリポソームベースのトランスフェクションによるマイクロニードルを介したsiRNAの送達 Microneedle-Mediated Delivery of siRNA via Liposomal-Based Transfection for Inner Ear Gene Therapy
Feng, Sharon J.; Voruz, François; Leong, Stephen; Hammer, Daniella R.; Breil, Eugénie; Aksit, Aykut; Yu, Michelle; Chiriboga, Lauren; Olson, Elizabeth S.; Kysar, Jeffrey W.; Lalwani, Anil K.
Otology & Neurotology Published:October 2024
DOI:10.1097/MAO.0000000000004297
Abstract
Hypothesis
Microneedle-mediated intracochlear injection of siRNA-Lipofectamine through the round window membrane (RWM) can be used to transfect cells within the cochlea.
Background
Our laboratory has developed 100-μm diameter hollow microneedles for intracochlear injection through the guinea pig RWM. In this study, we test the feasibility of microneedle-mediated injection of siRNA and Lipofectamine, a commonly used reagent with known cellular toxicity, through the RWM for cochlear transfection.
Methods
Fluorescently labeled scramble siRNA was diluted into Lipofectamine RNAiMax and OptiMEM. One microliter of 5 μM siRNA was injected through the RWM of Hartley guinea pigs at a rate of 1 μl/min (n = 22). In a control group, 1.0 μl of Lipofectamine, with no siRNA, was diluted into OptiMEM and injected in a similar fashion (n = 5). Hearing tests were performed before and either at 24 hours, 48 hours, or 5 days after injection. Afterward, animals were euthanized, and cochleae were harvested for imaging. Control cochleae were processed in parallel to untreated guinea pigs.
Results
Fluorescence, indicating successful transfection, was observed within the basal and middle turns of the cochlea with limited distribution in the apex at 24 and 48 hours. Signal was most intense in the organ of Corti, spiral ligament, and spiral ganglion. Little to no fluorescence was observed at 5 days post-injection. No significant changes in auditory brainstem response (ABR) were noted post-perforation at 5 days, suggesting that siRNA-Lipofectamine at low doses does not cause cochlear toxicity.
Conclusions
Small volumes of siRNA and Lipofectamine can be effectively delivered to cochlear structures using microneedles, paving the way for atraumatic cochlear gene therapy.
