b'4. Targeted Protein DegradationTargeted protein degradation (TPD) mediated by small molecule degraders intended to eliminate disease-causing proteins is another approach that continues to evolve. Biotechnology and large pharmaceutical companies are working on applying this transformativemodalitytowardsdrugdiscoveryandclinicalevaluation,either internally or via partnerships with researchers in the field. Significant advancements have been made in the discovery and development of clinically relevant degraders, and new assays, new technologies, and new screening modalities are being built to enable efficient and rational approaches.Still, there is much that remains to be fully understood. Efforts towards rational E3 ligase/target pairing, potency across cell types, impact of compound structural changestoternarycomplexkineticswithimpactonselectivity,andsteady-state degradation kinetics are areas that require more study. 5Understanding the relationship of in vivo degrader exposure to targeted protein degradation across tissues, and time (the pharmacokinetic-pharmacodynamic relationship) is one of the critical aspects, as the field works towards achieving clinical proof of concept.5 It will be essential for TPD research and fundamental findings to be shared in order to accelerate clinical evaluation of drugs based on this therapeutic modality.5.Oligonucleotide-Based Technique Most oligonucleotide (ON) therapies act through antisense mechanisms and are directed against various RNA species, as exemplified by gapmers, steric block ONs, antagomirs, small interfering RNAs (siRNAs), micro-RNA mimics, and splice-switching ONs. 6An important property of mRNAs is that the precise code they contain is specific to each protein. Therefore, antisense oligonucleotides can be designed to specifically target the production of protein from a single gene out of the many thousands in the human genome. And if the gene being targeted is mutated, just the mutant form of the gene can be precisely impacted. 7However, ONs binding to Toll-like receptors and those forming aptamers have completely different modes of action. 6'