S-540956, a CpG Oligonucleotide Annealed to a Complementary Strand With an Amphiphilic Chain Unit, Acts as a Potent Cancer Vaccine Adjuvant by Targeting Draining Lymph Nodes

Robust induction of cancer-antigen-specific CD8+ T cells is essential for the success of cancer peptide vaccines, which are composed of a peptide derived from a cancer-specific antigen and an immune-potentiating adjuvant, such as a Toll-like receptor (TLR) agonist. Efficient delivery of a vaccine antigen and an adjuvant to antigen-presenting cells in the draining lymph nodes (LNs) holds key to maximize vaccine efficacy. Here, we developed S-540956, a novel TLR9-agonistic adjuvant consisting of B-type CpG ODN2006 (also known as CpG7909), annealed to its complementary sequence oligodeoxynucleotide (ODN) conjugated to a lipid; it could target both a cancer peptide antigen and a CpG-adjuvant in the draining LNs. S-540956 accumulation in the draining LNs and activation of plasmacytoid dendritic cells (pDCs) were significantly higher than that of ODN2006. Mechanistic analysis revealed that S-540956 enhanced the induction of MHC class I peptide-specific CD8+ T cell responses via TLR9 in a CD4+ T cell-independent manner. In mice, the therapeutic effect of S-540956-adjuvanted with a human papillomavirus (HPV)-E7 peptide vaccine against HPV-E7-expressing TC-1 tumors was significantly better than that of an ODN2006-adjuvanted vaccine. Our findings demonstrate a novel adjuvant discovery with the complementary strand conjugated to a lipid, which enabled draining LN targeting and increased ODN2006 accumulation in draining LNs, thereby enhancing the adjuvant effect. Our findings imply that S-540956 is a promising adjuvant for cancer peptide vaccines and has a high potential for applications in various vaccines, including recombinant protein vaccines.

Design and Characterization of a Passive Wireless DNA Sensor

This paper presents a concept for a passive wireless DNA sensing platform that exploits a multidisciplinary area, synthesizing the conventional DNA capacitive sensing mechanism and the surface-based conformational characterization throughout DNA immobilization and hybridization. The resonant frequency shift, caused by the change of capacitance throughout DNA immobilization and hybridization and occurring on top of an interdigital capacitor, is monitored by means of an impedance analyzer. 32 samples were measured throughout the experiment and the average capacitance measurements represented a variety of surface charges resulting from DNA molecule immobilization and hybridization. The capacitance changed from 11.58 pF to 114.5 pF when specific ssDNA was attached to electrodes and then increased to 218.6 pF once complementary strand DNA was introduced and hybridized with existing DNA chains. In addition, using impedance analyzer measurements, the resonant frequency decreased from 2.01 MHz to 1.97 MHz in the presence of ssDNA and decreased further down to 0.95 MHz after the complementary strand DNA was deposited.

Points of View on the Tools for Genome/Gene Editing

Theoretically, a DNA sequence-specific recognition protein that can distinguish a DNA sequence equal to or more than 16 bp could be unique to mammalian genomes. Long-sequence-specific nucleases, such as naturally occurring Homing Endonucleases and artificially engineered ZFN, TALEN, and Cas9-sgRNA, have been developed and widely applied in genome editing. In contrast to other counterparts, which recognize DNA target sites by the protein moieties themselves, Cas9 uses a single-guide RNA (sgRNA) as a template for DNA target recognition. Due to the simplicity in designing and synthesizing a sgRNA for a target site, Cas9-sgRNA has become the most current tool for genome editing. Moreover, the RNA-guided DNA recognition activity of Cas9-sgRNA is independent of both of the nuclease activities of it on the complementary strand by the HNH domain and the non-complementary strand by the RuvC domain, and HNH nuclease activity null mutant (H840A) and RuvC nuclease activity null mutant (D10A) were identified. In accompaniment with the sgRNA, Cas9, Cas9(D10A), Cas9(H840A), and Cas9(D10A, H840A) can be used to achieve double strand breakage, complementary strand breakage, non-complementary strand breakage, and no breakage on-target site, respectively. Based on such unique characteristics, many engineered enzyme activities, such as DNA methylation, histone methylation, histone acetylation, cytidine deamination, adenine deamination, and primer-directed mutation, could be introduced within or around the target site. In order to prevent off-targeting by the lasting expression of Cas9 derivatives, a lot of transient expression methods, including the direct delivery of Cas9-sgRNA riboprotein, were developed. The issue of biosafety is indispensable in in vivo applications; Cas9-sgRNA packaged into virus-like particles or extracellular vesicles have been designed and some in vivo therapeutic trials have been reported.

6. Manufacturing and maintaining DNA

This chapter assesses DNA replication. The double-helix of DNA could easily be separated into two individual strands, each of which acts as a template for the manufacturing of a new complementary strand. This became known as semi-conservative replication, to indicate that each daughter DNA double-helix contained one new strand and one old strand, conserved from the parent molecule. Discovering the ways by which cells replicate their DNA led to the question: can we harness these amazing natural machines to shed light on DNA itself? The chapter then examines two key biotechnological advances: DNA sequencing and the polymerase chain reaction (PCR).

Polymorphism of Genetic Ambigrams

Double synonyms in the genetic code can be used as a tool to test competing hypotheses regarding ambigrammatic narnavirus genomes. Applying the analysis to recent observations of Culex narnavirus 1 and Zhejiang mosquito virus 3 ambigrammatic viruses indicates that the open reading frame on the complementary strand of the segment coding for RNA-dependent RNA polymerase does not code for a functional protein. Culex narnavirus 1 has been shown to possess a second segment, also ambigrammatic, termed ‘Robin’. We find a comparable segment for Zhejiang mosquito virus 3, a moderately diverged relative of Culex narnavirus 1. Our analysis of Robin polymorphisms suggests that its reverse open reading frame also does not code for a protein. We make a hypothesis about its role.

Steganographic Model for encrypted messages based on DNA Encoding

Information has become an inseparable part of human life. Some information that is considered important, such as state or company documents, require more security to ensure its confidentiality. One way of securing information is by hiding the information in certain media using steganography techniques. Steganography is a method of hiding information into other files to make it invisible. One of the most frequently used steganographic methods is Least Significant Bit (LSB).In this study, the LSB method will be modified using DNA Encoding and Chargaff's Rule. Chargaff's Rule or complementary base pairing rule is used to construct a complementary strand. The modification of the LSB method using DNA encoding and Chargaff's Rule is expected to increase the security of the information.The MSE test results show the average value of the LSB method is 0.000236368, while the average value for the DNA Encoding-based Steganography method is 0.000770917. The average PSNR value for the LSB method was 76.82 dB while the DNA Encoding-based Steganography method had an average value of 70.88 dB. The time of inserting and extracting messages using the Steganography method based on DNA Encoding is relatively longer than the LSB method because of its higher algorithmic complexity. The message security of the DNA Encoding-based Steganography method is better because there is encryption in the algorithm compared to the LSB method which does not have encryption.

Inhibition of thrombin activity by a covalent-binding aptamer and reversal by the complementary strand antidote

We created a DNA-aptamer-type covalent drug where the pharmacological effect can be reversed by the complementary strand antidote.

Minirmd: accurate and fast duplicate removal tool for short reads via multiple minimizers

Summary Removing duplicate and near-duplicate reads, generated by high-throughput sequencing technologies, is able to reduce computational resources in downstream applications. Here we develop minirmd, a de novo tool to remove duplicate reads via multiple rounds of clustering using different length of minimizer. Experiments demonstrate that minirmd removes more near-duplicate reads than existing clustering approaches and is faster than existing multi-core tools. To the best of our knowledge, minirmd is the first tool to remove near-duplicates on reverse-complementary strand. Availability and implementation https://github.com/yuansliu/minirmd. Supplementary information Supplementary data are available at Bioinformatics online.