Genetic Engineering Publications - GEG Tech top picks

Until now, researchers have lacked the tools to create a targeted cell therapy approach that could work on all the different forms of blood and bone marrow cancers. A new solution could solve a major problem in immunotherapy, namely the inability to target surface markers present on both cancerous and healthy cells. In the study, published today in Science Translational Medicine, researchers used CAR T cells engineered to target CD45, a surface marker present on almost all blood cells, including almost all blood cancer cells. Since CD45 is also found on healthy blood cells, the research team used CRISPR base editing to develop a method called "epitope editing" to overcome the challenges of an anti-CD45 strategy, which would otherwise result in potentially lethal low blood counts and threatening side effects. The modified version of CD45 still functions, but differs sufficiently from normal CD45 for anti-CD45 CAR T cells not to recognize and attack it. This study lays the foundations for a more universal approach that could potentially extend CAR T cell therapy to all blood cancers. 

In this article, the scientists  present an approach, called leveraging endogenous ADAR for programmable editing of RNA (LEAPER), that employs short engineered ADAR-recruiting RNAs (arRNAs) to recruit native ADAR1 or ADAR2 enzymes to change a specific adenosine to inosine. They pave the way for a single-molecule system, LEAPER, enabling precise, efficient RNA editing with broad applicability for therapy and basic research.

Immunotherapy is an essential component of cancer treatment. However, despite the success of immunotherapies for various types of cancer, only a few cancer patients have shown responses to current immune therapies and therapies can have adverse effects. Therefore, researchers have created intramuscular messenger ribonucleic acid (mRNA) lipid nanoparticle (LNP) vaccines as likely candidates for therapeutic cancer vaccines. RNA molecules can be encapsulated in LNPs. In addition, single-stranded mRNA can encode tumor vaccine neo-antigens, while small double-stranded interfering RNA can encode knockdown checkpoint inhibitors to adjust immune responses through RNA-induced activation of suppressed immune cells. Circular-type RNA can increase expression time, which benefits the generation of chimeric antigen receptors (CAR) in vivo and vaccine antigens. Targeted delivery of LNP in vivo would be essential for generating CAR-T macrophages and lymphocytes, in vivo. Based on the results of the study, the LNP mRNA vaccine platform could be used to develop next-generation personalized cancer vaccines. However, additional research is needed to further our understanding of cancer biology and improve vaccine design for faster clinical translation. 

Three studies in Science and Cell identify ∼2,000 essential genes in human cell lines using CRISPR-Cas9 and retroviral gene-trap genetic screens.