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MicroRNA mimics
MicroRNA mimics are artificial RNAs that are built upon naturally occurring microRNAs. The so-called
“passenger” strand of the mimic, which is not loaded into the RNA-induced silencing complex (RISC),
carries some mismatches; this is to prevent it from being loaded into RISC and to prevent its potential
[111]
action as an anti-microRNA .
Anti-microRNAs/AntagomiRs
Anti-microRNAs are oligonucleotides with sequences that are either entirely or partially complementary to
naturally occurring microRNAs. Consequently, this leads to blocking the interaction with the target genes
[106]
when they interact with the endogenous microRNA .
MicroRNA sponges
MicroRNA sponges are synthetic transcripts that contain multiple binding sites for microRNAs, which can
trap and sequester them . They can be designed to target one or many different microRNAs [113,114] . A study
[112]
by Jung et al. designed microRNA sponges that can sequester miR-155, miR-21, and miR-221/miR-222
within tumor-causing cells . Another study by Das et al. investigated the role of microRNA sponges
[115]
within myocardial infarction by designing anti-microRNA that can sequester a family of miR-181
[116]
microRNAs, which are miR-181a, miR-181b, and miR-181c .
MicroRNA masks
MicroRNA masks are oligonucleotides that are designed to conceal the microRNA binding regions of a
target gene. This prevents the microRNAs from carrying out their regulatory functions on that gene .
[117]
TYRP1 mRNA acts to sequester miR-16, inhibiting their tumor-suppressing functions within melanoma
cells. One study by Gilot et al. demonstrated the effects of blocking the microRNA binding site of TYRP1
[118]
mRNA, which caused the recovery of the cancer-suppressing function of miR-16 in melanoma tumors .
Small interfering RNAs
Small interfering RNAs (siRNAs) are short double-stranded molecules created by an enzyme called Dicer.
This enzyme cuts a long double-stranded RNA into smaller pieces known as siRNA, which are between 21
and 23 base pairs long and have a low molecular weight of around 14 kDa . They make use of the natural
[119]
[106]
endogenous microRNA pathway . A molecule of siRNA consists of both a sense and an antisense strand
that form complexes by binding to the RISC. The sense strand separates from the antisense strand with the
help of AGO-2. The antisense strand then guides the RISC to find a complementary mRNA, where it is then
cut by the AGO-2-RISC-siRNA complex, effectively stopping the translation process. They work by
initiating the process of breaking down mRNA, silencing specific genes, and reducing the levels of target-
[119]
specific proteins . Unlike antisense techniques, RNAi uses a catalytic mechanism for its action, where
siRNA-loaded RISC can dissociate and bind to other mRNA molecules after the target mRNA is cleaved.
This is why it is effective at very low concentrations of siRNA in the picomolar range, which can efficiently
knock down genes, and it has been found that intracellular amounts of less than 2,000 siRNAs per cell are
enough to achieve this effect. It is also important to note that the siRNA mechanism is different from that of
microRNAs, which bind to their targets with only partial complementarity, whereas siRNA action requires
100% complementarity .
[120]
Short hairpin RNAs
Short hairpin RNAs are single-stranded RNAs made up of two sets of complementary sequences on the
same strand, known as “sense” and “antisense” sequences, that are 19-22 nucleotides in length. These
sequences contain a short loop consisting of 7 to 9 nucleotides that are not bonded, which enables them to
form a hairpin shape . The main function of short hairpin RNAs is to produce double-stranded siRNAs
[109]