Photocontrolled apoptosis induction using precursor miR-664a and an RNA carrier-conjugated with photosensitizer
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Published on: February 17, 2023
Kazunori Watanabe1,2, Tomoko Nawachi3, Ruriko Okutani4
1Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, 3-1-1 Tsushimanaka, Okayama, 700-8530, Japan. k_watanabe@okayama-u.ac.jp.
Abstract:
Methods to spatially induce apoptosis are useful for cancer therapy. To control the induction of apoptosis, methods using light, such as photochemical internalization (PCI), have been developed. We hypothesized that photoinduced delivery of microRNAs (miRNAs) that regulate apoptosis could spatially induce apoptosis. In this study, we identified pre-miR-664a as a novel apoptosis-inducing miRNA via mitochondrial apoptotic pathway. Further, we demonstrated the utility of photoinduced cytosolic dispersion of RNA (PCDR), which is an intracellular RNA delivery method based on PCI. Indeed, apoptosis is spatially regulated by pre-miR-664a and PCDR. In addition, we found that apoptosis induced by pre-miR-664a delivered by PCDR was more rapid than that by lipofection. These results suggest that pre-miR-664a is a nucleic acid drug candidate for cancer therapy and PCDR and pre-miR-664a-based strategies have potential therapeutic uses for diseases affecting various cell types.
Insights
Researchers developed a new method using light to deliver apoptosis-inducing microRNAs (miRNAs) for cancer therapy. This photoinduced delivery of pre-miR-664a offers a rapid and spatially controlled way to induce cell death.
Area of Science:
- Molecular Biology
- Biotechnology
- Cancer Research
Background:
- Spatially controlled induction of apoptosis is crucial for effective cancer therapy.
- Light-based methods like photochemical internalization (PCI) offer precise control over cellular processes.
Purpose of the Study:
- To investigate the potential of photoinduced delivery of apoptosis-regulating microRNAs (miRNAs) for spatial apoptosis induction.
- To identify novel apoptosis-inducing miRNAs and evaluate a new intracellular RNA delivery method.
Main Methods:
- Identification of pre-miR-664a as an apoptosis-inducing miRNA through the mitochondrial pathway.
- Utilizing photoinduced cytosolic dispersion of RNA (PCDR), an intracellular RNA delivery system based on PCI.
- Comparing the speed of apoptosis induction by pre-miR-664a delivered via PCDR versus lipofection.
Main Results:
- Pre-miR-664a was identified as a novel miRNA that induces apoptosis via the mitochondrial pathway.
- Photoinduced cytosolic dispersion of RNA (PCDR) was successfully employed for intracellular delivery of pre-miR-664a.
- Apoptosis was spatially regulated by the combination of pre-miR-664a and PCDR.
- PCDR-mediated delivery of pre-miR-664a resulted in more rapid apoptosis induction compared to lipofection.
Conclusions:
- Pre-miR-664a is a promising nucleic acid drug candidate for cancer therapy.
- The PCDR method and pre-miR-664a-based strategies show potential for treating diseases involving various cell types.
- This approach offers a novel, light-controlled method for inducing apoptosis with therapeutic implications.
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