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Low back pain (LBP) affects an overwhelming majority of the population. It is a leading cause of disability worldwide and an enormous socioeconomic burden to individuals and their families, only second to cancer. Just under half of LBP is attributed to intervertebral disc (IVD) degeneration. IVD degeneration is characterized by decreased cellularity, decreased proteoglycan, increases in matrix-degrading enzymes (MMPs) and pro-inflammatory factors, as well as neurovascular invasion. The annulus fibrous (AF) is one of three main components of the IVD. This section of tissue is crucial to the IVD's structural integrity and healthy performance, yet it is understudied and under targeted compared to the center portion of the IVD known as the nucleus pulposus (NP). The AF experiences degenerative changes that inhibit functionality and can be detrimental to a person's quality of life. Novel therapeutic strategies may be able to slow down, or even reverse, the progression of IVD degeneration. Transcription factors are proteins that play a role in regulating transcription within a cell and may help promote a desired cellular phenotype. Mohawk (MKX) and Scleraxis (SCX) are two transcription factors highly expressed in healthy AF cells, contributing to the development, maintenance, regeneration, and anti-angiogenic properties of the AF. Regenerative therapies, such as cellular therapy or viral gene delivery, have limited clinical potential due to cell survivability, unwarranted immune response, and mutagenesis. We hope that non-viral transfection via bulk electroporation will bypass these caveats while successfully delivering MKX/SCX into degenerate AF cells, promoting a healthy, pro-anabolic AF cell phenotype. Following transfection, the AF cells were assessed for cell morphology, gene expression, and extracellular matrix (ECM) content. These parameters were assessed to provide information regarding the cellular processes, characteristics, and associated health state. We hypothesized that MKX/SCX will increase anabolic phenotypic markers, decrease catabolic/inflammatory markers, and enhance ECM quantity and composition compared to controls. After completing the necessary experimentation and analyzing the extracted data, it was found that the degenerate AF cells demonstrated an elongated fibroblast-like morphology, pro- anabolic/anti-catabolic gene expression, and increased synthesis/accumulation of collagen. This demonstrates the efficacy of in-vitro non-viral transfection of MKX and SCX in AF cells and illuminates the promise of implementing these two transcription factors in future therapeutics that target AF to ideally stop/reverse the progression of IVD degeneration and associated LBP.