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Table 1 Comparison between the cytoplasmic RNA viruses and the currently used RNA and DNA viruses for RNAi-based therapy

From: Cytoplasmic RNA viruses as potential vehicles for the delivery of therapeutic small RNAs

Genus

Main representative

Genome(sense)

Genome size (Kb)

Immuno-genicity

Expression level

Genomic insertion

Time of expression

Advantages

Limitations

Alphavirus

Sindbis virus

ssRNA (+)

12

High

High

No

Short-term

- Cytoplasmic replication allowing high expression levels and potential non-canonical processing of artificial miRNAs.

Toxicity due to viral replication (non-cytopathic vectors overcome this limitation)

- Apoptosis induction, they can be considered in Cancer gene therapy applications.

- Infect neurons in primary and cell lines, could be good candidates for gene therapy in Central Nervous System (CNS)

Flavivirus

West Nile virus, Tick-borne encephalitis virus

ssRNA (+)

11

Medium

High

No

Short-term

- Cytoplasmic replication allowing high expression levels and potential non-canonical processing of artificial miRNAs.

Toxicity (non-cytopathic vectors available Pre–existing immunity mainly in (sub)tropical countries

- Genetic structure allow easy manipulation

Vesiculovirus

Vesicular stomatitis virus

ssRNA (-)

11

High

High

No

Short-term

- Cytoplasmic replication allowing high expression levels and potential non-canonical processing of artificial miRNAs.

Very sensitive to the antiviral action of interferon

- Apoptosis induction, they can be considered in cancer therapy

Lentivirus

Human immunodeficiency virus type 1

ssRNA (+)

8

Low

High

Yes

Long-term

Persistent gene transfer in most tissues

Integration might induce oncogenesis

Dependovirus

Adeno-associated virus serotype 2

ssDNA

<5

Low

High

Yes

Long-term

Non-pathogenic parental viruses

Integration might induce oncogenesis

Herpesvirus

Herpes simplex virus type 1

dsDNA

150

High

High

No

Short-,Medium-term

Well suited as oncolytic vector and CNS applications (retrograde axonal transport)

Risk of recombination with latently herpes simplex virus-infected cells