Transcription factors(TFs) play the fundamental role as molecular codes in maintaining the cellular identity and homeostasis . The modern sequencing techniques and ‘Omics’ tools have been accumulating a massive wealth of biological information about the cell fate-regulating TFs and the association of defective TFs with complex diseases. Still, there is a considerable gap between the accumulated knowledge database and the available tools to modulate them. A closer look at the coordinated control existing in the natural cellular environment could aid us in achieving synthetic TFs that could mimic the irnatural counterparts in terms of structure and function. Inside the living cells, genetic and epigenetic programs precisely orchestrate the intricate molecular network by switching “ON” and “OFF” the transcription program at the right place and time. Although small molecules targeting the signaling proteins and epigenetic programs could reset gene transcription machinery , they lack the defining feature of a TF i.e., DNA - binding domain . Because both patients and clinicians favor the use of small molecules over biological drugs, there is a growing demand to create genetic knowledge based small molecules as synthetic TF mimics. Hairpin pyrrole - imidazole polyamides (PIPs) are the selective DNA-binding small molecules that could be pre-programmed to read specific DNA sequences. Taking cues from nature, our group has been developing the designer PIPs and different functional conjugates as biomimetic synthetic molecular codes to turn genes ON and OFF. Our programmable synthetic molecular codes triggered promoter-specific transcription suppression of oncogenes and reversed the tumor growth in a mouse model by targeting the point mutations. [1] Recently, we also created first -ever mitochondrial gene switch called MITO-PIP that could precisely switch OFF mitochondrial genes on demand inside the living cells. [2]By taking the critical role of epigenome into account, we also created biomimetic epigenetic codes by conjugating designer PIPs with synthetic modulators of epigenetic enzymes and scripted epigenetic activation of genes and non-coding RNAs associated with germ cells, stem cells, retinal cells, Alzheimer’s, HIV, autism and obesity. [3-6]Also, we harnessed the knowledge about the cell fate regulating TFs and scripted the targeted differentiation of stem cells into either cardiomyocytes [7] or neurons. Advancing our synthetic molecular codes could open new vistas of opportunities in therapeutic gene modulation and regenerative medicine.