Bio-Synthesis Newsletter - September 2019

A Taxol conjugate kills cancer in mice

Conjugating drugs to fatty acids which cells can quickly metabolize for energy can trick cancer cells into taking up conjugated drug molecules. However, it has been challenging for a chemist to develop a reliable fatty acid-based drug-delivery system . Recently, a research team at Northwestern University developed a drug-delivery system by conjugating 1,18-octadecanedioic acid to Paclitaxel (taxol) called ODDA-PTX. The chemotherapeutic drug Paclitaxel stops dividing tumor cells.The new fatty acid–drug conjugate binds to blood albumin in small pockets on its surface and is actively taken up by dividing cancer cells preventing the tumor cells from dividing after binding to microtubules. (J. Am. Chem. Soc. 2019, DOI: 10.1021/jacs.9b04272).

The promise of CRISPR/Cas9 based Genome Editing

Mutations in our genome are known as the cause of many human diseases. The development of the recently discovered CRISPR gene editing system allows directed cleavage of the cellular genome at any location with the help of modifying guide RNA. More recently, CRISPR based chips have been developed useful as Genomic Sensors to “google genomes” using guide RNAs. Since CRISPR systems can cause off-target effects that can be inherited in the germline, using CRISPR for gene editing in humans has become a controversial subject. Therefore a more precise CRISPR system may need to be developed. Incorporating modified oligonucleotide into a guide or tracer RNA such as BNA oligonucleotides that have lesser toxicity than other modified nucleotides could allow achieving this goal.

Peptides allow vaccination for Peanut Allergy

Australian researchers recently developed a peptide-based vaccine as an injection-based therapy for peanut allergies and are hopeful that the new vaccine will work efficiently. The new peptide vaccine consists of a mixture of small, synthetic peptides derived from peanut protein allergen sequences. The peptides do not contain parts of peanut proteins that can set off anaphylactic reactions. Presumably, the peptides retrain peanut-specific T-cells to induce tolerance and be reprogrammed immune cells that cause allergy to become tolerant. Furthermore, the synthetic peptides don’t bind to IgE an antibody, which minimizes the risk of the adverse reactions. Biosynthesis Inc. can help you with the development of peptide-based vaccines

DNA methylation and Cancer Diagnostics

Worldwide, cancer causes the most deaths; however, when detected, early modern therapies often can cure common diseases. Therefore translational medicine aims to develop reliable and cost-effective detection methods for early detection of tumors. In cancers, loss of expression of genes occurs about ten times more frequently by hypermethylation of promoter CpG islands than by mutations. For example, in colorectal cancer, there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. DNA damage and the deregulation of gene expression appear to be the primary underlying cause of cancer. Epigenetic modifications play a significant role in the development of most cancers that classified into three processes: DNA methylation, histone modification, and chromatin remodeling. DNA methylation is a specific genome alteration that may be a significant cause of cancer as well as other genetic changes. DNA methylation mainly occurs at cytosine molecules. CpG methylated oligonucleotides in genomic DNA are new biomarkers useful for cancer diagnostics. Furthermore, synthetic methylated CpG oligonucleotides may turn as being useful for the development of diagnostic tools.

Please note that creation and use of synthetic oligos for CRISPR applications requires a license from ERS genomics, the holders of IP for CRISPR technology. We do not have a license to provide synthetic oligos used in CRISPR technology from ERSGenomics. Contact ERSGenomics.com for further information.