Table 1 Key examples of site directed RNA editing

A-to-I

Exogenous ADAR based

λN-BoxB

The small size allows for adeno-associated virus-based delivery.

Low editing efficiency and some bystander editing.

[38, 141, 142]

SNAP-ADAR

Human origin, small size, chemically stabilized gRNAs are ease to transfect.

It isn’t genetically encodable and unlikely to have therapeutic value.

[143, 144]

WT ADAR2

Simultaneous expression of gRNA and ADAR2 in a single plasmid are enough to manipulate disease-related cellular phenotypes.

Can lead to significant transcriptome-wide off-targeting.

[145]

REPAIR

High editing specificity and easy to viral delivery.

Massive bystander editing.

[146]

Split-ADAR

High editing precision. Tunable and reversible engineering of cellular RNAs for diverse applications.

Interferon response by the delivery modalities.

[147,148,149]

Bump-Hole

High efficiency and low off-target editing.

With the risk of an antidrug response to the ADAR2 E488Y mutant.

[150]

CIRTS

It is small in size, suitable for efficient viral packaging and delivery. Low propensity to cause immune reactions.

NA

[151, 152]

REWIRE

Small size, entirely originated from human, and can be independently applied to achieve simultaneous A-to-I and C-to-U editing in the same transcript.

The editing efficiency RNAs in animals still needs to be optimized.

[153]

TRIBE

It is beneficial for labelling target RNAs that long-lived interact with RBPs.

The efficiency of single-stranded RNA is reduced, and the substates bias of ADARcd can lead to false negatives.

[154, 155]

Endogenous ADAR based

RESTORE

The editing is achieved only through the administration of the ASOs.

Some degree of off-target.

[152, 156]

LEAPER

It is safe and the circularization improves the expression level of the gRNA.

A substantial bystander of off-target editing.

[157, 158]

AIMers

Short, chemically modified oligonucleotides can guide efficient and specific RNA editing.

NA

[159]

CLUSTER

High precision RNA editing and the editing homeostasis at natural sites was untouched.

Potential immunogenetic or toxic effects of these highly expressed gRNA species.

[160]

Caged arASO for light triggered RNA editing

Light-triggered RNA point mutation of transcripts in human cells exhibit spatial photoregulation.

Achieving A-to-I editing in CDS of mRNA requires a longer antisense domain.

[161]

RADARS

Specificity, versatility, simplicity, and generalizable across organ systems and species.

The detection of endogenous transcripts showed variable results.

[162, 163]

C-to-U editing

Exogenous engineered ADAR based

RESCUE

Expands the RNA targeting arsenal with C-to-U functionality, and easy for delivery

Accidental transcriptome A-to-I deaminaton limit potential therapeutic uses.

[164]

RESCUE-S

Minimize the off-target A-to-I conversions.

Reduced on-target C-to-U editing efficiency.

[165]

SNAP-CDAR-S

Improved the editing of the context of 5’-CCN sequence and improved on-target editing.

There are still notably frequent off-target of A-to-I edits.

[144, 166]

Endogenous APOBEC based

CURE

Both cytoplasmic and nuclear transcripts could be edited.

The strict codon preference and the potential to induce off-target edits in DNA.

[165]

REWIRE

The editing rate of human cells is high, with a few non-specific editing sites and low levels of off-target globally.

Sequences similar to PUF domain recognition sites may be non-specifically edited.

[153]