A5049348828- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA regulation and disease
- Antimicrobial Peptides and Activities
- Neonatal Respiratory Health Research
- Trace Elements in Health
- Respiratory viral infections research
- MicroRNA in disease regulation
- Porphyrin Metabolism and Disorders
University of Massachusetts Chan Medical School
2016-2022
University of Southampton
2016-2018
Abstract RNA-based drugs depend on chemical modifications to increase potency and decrease immunogenicity in vivo. Chemical modification will likely improve the guide RNAs involved CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. Here, we explore at all positions of crRNA tracrRNA cofactor. We identify several heavily modified versions more potent than their unmodified counterparts. In addition, describe fully chemically crRNAs...
RNA-based therapeutics are emerging as a powerful platform for the treatment of multiple diseases. Currently, two main categories nucleic acid therapeutics, antisense oligonucleotides and small interfering RNAs (siRNAs), achieve their therapeutic effect through either gene silencing, splicing modulation or microRNA binding, giving rise to versatile options target pathogenic expression patterns. Moreover, ongoing research seeks expand scope drugs include more complex templates, such messenger...
The lung is a complex organ with various cell types having distinct roles. Antisense oligonucleotides (ASOs) have been studied in the lung, but it has challenging to determine their effectiveness each type due lack of appropriate analytical methods. We employed three approaches study silencing efficacy within different types. First, we used lineage markers identify flow cytometry, and simultaneously measured ASO-induced cell-surface proteins CD47 or CD98. Second, applied single-cell RNA...
Two mechanisms dominate the clinical pipeline for oligonucleotide-based gene silencing, namely, antisense approach that recruits RNase H to cleave target RNA and RNAi RISC complex RNA. Multiple chemical designs can be used elicit each pathway. We compare silencing of asthma susceptibility ADAM33 in MRC-5 lung fibroblasts using four classes agents, two use mechanism: traditional duplex small interfering RNAs (siRNAs), single-stranded (ss-siRNAs), locked nucleic acid (LNA) gapmer...
Single-stranded silencing RNAs (ss-siRNAs) are chemically modified single-stranded oligomers that engage the RNA interference machinery normally used by duplex to silence gene expression. ss-siRNAs have potential combine advantages of antisense oligonucleotides and siRNAs. Previous work has explored chemistry phosphate oligonucleotide body. We now describe process attempting develop optimize based on five active siRNA duplexes. Three sequences failed show any activity as ss-siRNAs, in two...
We present a new design of mixed-backbone antisense oligonucleotides (ASOs) containing both DNA and peptide nucleic acid (PNA). Previous generations PNA–DNA chimeras showed low binding affinity, reducing their potential as therapeutics. The addition 5′-wing locked well the combination modified nucleotide PNA monomer at junction between yielded high-affinity chimeras. resulting ASOs demonstrated high serum stability elicited robust RNase H-mediated cleavage complementary RNA. These properties...
RNA-based drugs depend on chemical modifications to increase potency and nuclease stability, decrease immunogenicity in vivo . Chemical modification will likely improve the guide RNAs involved CRISPR-Cas9-based therapeutics as well. Cas9 orthologs are RNA-guided microbial effectors that cleave DNA. No studies have yet explored at all positions of crRNA tracrRNA cofactor. Here, we identified several heavily-modified versions more potent than their unmodified counterparts. In addition,...
Abstract Small activating RNAs (saRNAs) are short, double-stranded oligonucleotides designed to specifically upregulate target mRNA and protein expression by loading into an Ago2 complex for nuclear translocation activation of RNA polymerase II activity. We have developed MTL-CEBPA, saRNA-based therapeutic increase the CEBPA transcription factor that acts as both a tumor suppressor key modulator microenvironment. In preclinical models MTL-CEBPA has single-agent antitumor activity very...