Nucleic Acid-based Small Molecules as Targeted Transcription
Therapeutics for Immunoregulation
Abstract
Transcription therapy is an emerging approach that centers on
identifying the factors associated with the malfunctioning gene
transcription machinery that causes diseases and controlling them with
designer agents. Until now, small molecule drugs targeting the
epigenetic enzymes and critical signaling pathways have been the primary
research focus in therapeutic gene modulation. However, nucleic
acid-based small molecules have gained popularity in recent years as
they could be pre-designed on demand to achieve operative control over
the dynamic transcription machinery that governs how the immune system
responds to diseases. Pyrrole-imidazole polyamides (PIPs) are
well-established DNA-based small molecule gene regulators that overcome
the limitations of their conventional counterparts owing to their
sequence-targeted specificity, versatile regulatory efficiency and
biocompatibility. Here, we emphasize the rational design of PIPs, their
functional mechanism and their potential as targeted transcription
therapeutics for diseases by regulating the immune response.
Furthermore, we also discuss the challenges and foresight of this
approach in personalized immunotherapy in precision medicine.