Oligonucleotide-directed targeting to regulate gene function has enabled genome-wide studies and extended to the hope of targeting any gene. We will discuss the optimization of guide RNA synthesis for CRISPR activation (CRISPRa) which requires substantially longer oligonucleotides.  CRISPRa is the most promising new technology for overexpression, synthesis of CRISPRa guides has allowed rapid evaluation of large gene families.  

Join SCIEX analytical technology experts Matthew Stone and Mukesh Malik during an interactive Q&A session to discuss analytical development and optimization of capillary electrophoresis and liquid chromatography-mass spectrometry based methods for protein characterization and quantification. Exciting topics covered include mAbs and mAb variants, cell and gene therapy, vaccines and more!

RNAi enables simple and specific modulation of gene expression when the chemical architecture supporting efficient in vivo delivery is defined. Using huntingtin – the causative gene in Huntington disease – as a model, we demonstrate that chemically engineered siRNAs induce potent protein silencing (> 99%) in all brain regions tested one month post injection. Further chemical optimization enables broad distribution and silencing in large-brain animal models.

MicroRNAs are short non-coding RNAs that regulate biochemical pathways by RNA interference (RNAi). Dysregulation of microRNAs is associated with many diseases. MicroRNA-21 has been implicated with fibrotic diseases and cancer. The presentation shows the development of an anti-fibrotic antisense oligonucleotide (anti-miR-21) for the treatment of a genetic fibrotic kidney disease called Alport Syndrome, and summarizes the potential of anti-miR-21 as a drug to treat hepatocellular carcinoma.

We will give an overview of sample preparation strategies for synthetic oligonucleotides, including how to adjust experimental design depending on the oligo and sample matrix. We will we go in depth into the parameters to adjust to ensure an effective sample prep and cleanup is implemented and approaches for other challenging oligos which are unique in that they do not have the negatively charged backbone associated with other nucleic acid chemistries.

Polyoma BK virus (BKV) is a highly prevalent latent renal virus that can cause major clinical
issues for immunocompromised patients, which include patients undergoing hematopoietic
stem cell transplantation or kidney transplantation. Although the clinical manifestations may
present slightly differently, both populations are at risk of BKV-associated nephropathy and
graft loss, as well as immediate and severe symptoms such as hemorrhagic cystitis and/or
renal dysfunction. There are currently no treatments for combating BK virus. As such, novel
treatment strategies to limit BKV reactivation are vital. Hybridize has developed an
innovative RNA-based strategy to combat BKV-mediated disease and in this presentation
we will show our approach in abrogating viral DNA replication as well as capsid protein
formation.

Antibody oligonucleotide conjugates (AOCs^TM) deliver oligonucleotide therapeutics to multiple cell and tissue types, expanding the therapeutic utility of oligos by combining selective binding of antibodies and specificity of oligonucleotides. Design and engineering AOCs require optimization of the antibody, the oligonucleotide, and the linkers. Taking each of the optimized parts and then optimizing them has enabled us to deliver AOCs to multiple cells and tissues using multiple cell surface-mAb pairs.

Innovative vaccine delivery technologies will be presented including single-injection self-boosting vaccines, 3D printed on-demand micro-needle mRNA vaccines and on patient medical records using invisible dyes.