Table 2.
The advantages and disadvantages of different methods targeting circRNA therapeutics
| Pattern | Technology | Material | Effect | Advantages | Disadvantages |
|---|---|---|---|---|---|
| In vitro | RNAi | ShRNA, siRNA, ASO. | KD |
1. Convenient to synthesis and deliver; 2. Relative low expense. |
1. Rapid degradation; 2. Low delivery efficiency; 3. Lack of cell-specificity; 4. Off-target effect. |
| In vivo &vitro | CircRNA expression vector | Plasmid, LV, AAV. | OE & KD |
1. Relative stable; 2. Frequently used. |
1. Mis-spliced product; 2. Off-target effects. |
| In vivo & vitro | Synthetic circRNA | Circularized RNAs | OE | Highly purified. |
1. Difficult to generate large amount; 2. Immune system activation. |
| In vivo | Nanoparticle | Liposome, polymer, dendrimer, inorganic material (gold, or metal oxides). | OE & KD |
1. Target specific cell through receptors and ligands; 2. Relatively stable from degeneration; 3. Facilitate cell uptake; 4. Prevent to immune activation. |
1. Limited to target to the cytoplasmic circRNAs; 2. Low delivery efficiency; 3. Toxicity. |
| In vivo &vitro | Exosome | Exosome | OE & KD |
1. Protect RNAi molecules from degradation; 2. Promote cellular uptake; 3. Biocompatible. |
1. Difficult in manufacturing; 2. High cost. |
| In vivo | Cre-lox system | Cre recombinase | KO |
1. Cell-type specific or tissue specific; 2. Relatively safe. |
1. Ectopic Cre expression leads to the off-target effect; 2. Need validation of genotyping. |
RNAi RNA interfering, shRNA Short hairpin RNA, siRNA Short interfering RNA, ASO Antisense oligonucleotides, LV Lentivirus, AAV Adenovirus-associated virus, OE Overexpression, KD Knock-down, KO Knock-out