Hole transfer processes between base pairs in natural DNA and size-expanded DNA (xDNA) ire studied and compared, by means of ail accurate first principles evaluation of the effective electronic couplings (also known as transfer integrals), in order to assess the effect of the base augmentation on the efficiency of charge transport through double-stranded DNA, According to our results, the size expansion increases the average electronic coupling, and thus the CT rate, with potential implications in molecular biology and in the implementation of molecular nanoelectronics. Our analysis shows that the effect of the nucleobase expansion oil the charge-transfer (CT) rate is sensitive to the sequence of base pairs. Furthermore, we find that conformational variability is an important factor for the modulation of the CT rate. From a theoretical point of view, this work offers a contribution to the CT chemistry in pi-stacked arrays. Indeed, we compare our methodology against other standard computational frameworks that have been adopted to tackle the problem of CT in DNA, and Unravel basic principles that Should be accounted for in selecting ail appropriate theoretical level.