Smallest group size for differential expression in limma (bulk RNA-Seq)
The problem with most of the methods is that use the gene's variance for each group, which can't be calculated (reliable) when the sample is &lt;= 2. Also, statistically, it would have extremely low power, so the conclusions couldn't be trusted much. 

You could also calculate the "raw" fold change by yourself (ie without the variance estimation and adjusting). If you had one more sample per group you could use DESeq2 which was thought for such cases. But from the paper:


  However, if there are two or fewer replicates for a condition, these samples do not contribute to outlier detection, as there are insufficient replicates to determine outlier status.


Which makes me unsure if it will work well for just two samples as it won't help to detect outliers genes.