Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR‐associated protein 9 (CRISPR‐Cas9) is a genome editing tool that can remove, modify, or add sections of DNA. It is made up of two main molecules: the Cas9 protein and the guide‐RNA (gRNA), which is used to match a target gene to the CRISPR‐Cas9 molecule. The desired sequence of DNA must be between 2 and 5 nucleotides and must be followed by the protospacer adjacent motif (PAM) at the 3’ end of the gRNA. This enables the target gene to be found and cut by the Cas9 endonuclease. Once cut, the DNA can be repaired using non‐homologous end joining (where a random insertion or deletion of DNA occurs) or homology directed repair (where a homologous piece of DNA is used as a template to repair the DNA). The latter is used for genome editing, as the target sequence can be changed with the CRISPR‐Cas9 system. Sickle Cell Disease (SCD) is an autosomal recessive hereditary disorder that affects erythrocytes and is caused by a single base substitution of adenine to thymine on the hemoglobin beta (HbB) gene. Currently two different groups are examining two different techniques to treat SCD. One group has shown that by deleting the BCL11A gene, fetal hemoglobin production can occur, which greatly diminishes the amount of Sickle hemoglobin (HbS). An example of this application of CRISPR‐Cas9 for treating SCD is the story of Victoria Gray, the first person to have received genome editing treatment for SCD.

X‐linked inhibitor of apoptosis protein (XIAP) is a key prosurvival protein that blocks apoptosis by inhibiting both the intrinsic and extrinsic pathways. Released by the mitochondria when under stress, XIAP is a homodimer, with 2 sets of repeating type I and type II baculoviral IAP domains: BIR1, BIR2 and BIR3, and RING. XIAP has a capacity to block apoptosis by directly inhibiting caspases 3,7 and 9. Second mitochondria‐derived activator of caspases (Smac) is a 184 amino acid chain. Smac antagonizes XIAP by attaching to the BIR3 domain inhibiting the binding of caspase‐9. Synthetic Smac mimetics (SMs) have been designed to duplicate the N‐terminal tetrapeptide (AVPI) or the IAP‐binding motif (IBM). Our model aims to show two BIR3 domain of a homodimer XIAP, bound to the IAP‐binding motif (IBM) of a Smac dimer. Selective antagonism of XIAP, specifically the BIR3 by Smac/SMs or monotherapy is not enough to kill cancer cells, however, it could be combined with immunotherapy, specifically virotherapy. This tricks the immune system to think that the cancer cells have a virus, which stimulates the immune antiviral response and creates an overproduction of immune cells known as a “cytokine storm”, to kill cancer cells. Support or Funding Information The Ashbury College MSOE Center for BioMolecular Modeling SMART Team used 3D modeling and printing technology to examine structure‐function relationships between Smac and BIR3 of XIAP.