Swine are used throughout the biomedical community as translational research models, due to their physiological similarity to humans. However commercial swine are bred for consumption, therefore bigger is better, which is not always beneficial to the scientific community, in terms of maintenance costs. To generate pigs of reduced size, the current study utilized RNA interference to knockdown the high mobility group AT-hook 2 (HMGA2) gene. Three short hairpin RNA sequences (shRNA; SH1, SH2, and SH3) targeting HGMA2 were inserted into the pLKO.1 vector, a vector used by the RNAi Consortium to produce their shRNA library. A scrambled shRNA was used to control for off-target effects. Expression levels of HMGA2 mRNA in porcine fetal fibroblasts were analyzed by quantitative real-time polymerase chain reaction and the experiment was replicated three times. Results indicate that SH1 and SH3 were able to significantly (P<0.05) reduce the level of HMGA2 mRNA by 71% and 78%, respectively. Future work will focus on whether the knockdown of HMGA2 is proportional to adult pig size, since Zhou et al. produced a pygmy mouse model by deleting the HMGA2 gene.