CRISPR/Cas9 system is a RNA guided DNA nuclease that presents a powerful tool for genome editing due to its simple engineering, fixability and versatility. Important applications such as generation of disease animal model and treatment of genetic disorders require specific targeting and engineering in vivo. Several types of synthetic nanoparticles (NPs) have been developed to overcome the mentioned limitations. While NPs enhances CRISPR/ Cas9 stability during circulation, NPs can be identified and cleared by mononuclear phagocyte system (MPS). Natural Megakaryocytes microparticles ( Mk-MPs) is produced by Megakaryocytes and interact with Hemopoietic stem cells (HSCs), inducing their differentiation to Megakaryocytes. HSCs are rare multi-potent cells that possess ability to self-renew and differentiate to progenitor cells, which give rise to all blood cell lineages. Prof. Niveen have a record of successful ex-vivo and in vivo genome engineering delivered by ZIF-8 NPs coated by cell membrane). We want to use isolated Megakaryocyte membrane to coat ZIF-8 NPs to deliver and carry out targeted genome engineering in HSCs. We will prepare CRISPR/Cas9 encapsulated ZIF-8 and coat it with Megakaryocytes membrane. Then, we will characterize coated nanoparticles. Next, Test encapsulated CRISPR/Cas9 efficiency and specificity for a targeted HSCs target gene in vitro. Following, we will investigate CRISPR/Cas ZIF-8 NPs delivery and efficiency using cell lines and animal models.