Abstract
Purpose :
Spherical nucleic acids (SNAs) are densely packed, radial arrangements of oligonucleotides around a nanoparticle core. As a consequence of their structure, SNAs have increased cellular uptake, nuclease stability, and affinity to targets compared with linear oligonucleotides. Our previous studies showed that SNAs substantially increase distribution and persistence in local tissues of GI tract, lung, skin, and CNS compared to linear oligonucleotides following oral, inhalation, topical, and intrathecal administration, respectively. Here, we compared biodistribution of SNAs and linear oligonucleotides in rat eyes following intravitreal injection.
Methods :
Cy5-labeled SNA and linear oligonucleotide were synthesized and injected intravitreally into Brown Norway rat eyes at two dose levels. The Cy5-labeled SNA and linear oligonucleotides in the ocular tissues were profiled by fluorescence microscopy analysis for distribution, Cy5-signal intensity, and cellular uptake.
Results :
SNAs showed a dose- and time-dependent distribution to both posterior and anterior tissues, including retina, cornea, and ciliary body/iris. SNA showed 100% retinal coverage compared to linear oligonucleotide that has shown less than 50% retinal coverage at the same dose level and time point. SNA-associated fluorescence signal persisted over time in eye tissues. In contrast, linear oligonucleotide signal decreased rapidly by 24 hr. Mild or minimal inflammation was observed with either compound, which was comparable to that observed in the vehicle injected rat eyes.
Conclusions :
SNA distributes at higher levels to both posterior and anterior ocular structures and persists longer compared to linear oligonucleotide following intravitreal injection into rat eyes. SNA structure does not cause inflammation in the eye and has greater potential for targeting retinal and corneal eye diseases.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.