Technology

NeuBase is accelerating the genetic revolution using its proprietary Peptide-nucleic acid AnTisense OLigo (PATrOL) platform.

Modular and highly specific, the PATrOL platform has the potential to significantly improve upon current gene modulation technologies by combining the specificity of nucleotide engagement with the intracellular penetration and broad organ distribution capabilities of small molecule therapeutics.

Accelerating the Genetic Revolution

Key features of our PATrOL-enabled therapies include:

  • Modular molecular design
  • Biologically and immunologically inert
  • Resistant to degradation in the body
  • High specificity for target genes while minimizing off-target engagements (OTEs)
  • Broad distribution throughout all tissue types
  • Ability to use many chemistries for tissue and cell-type specific delivery
  • No toxic intramolecular aggregation due to semi-rigid scaffold
  • Potential to address dominant and recessive genetic diseases
  • Ability to open up and bind to double-stranded nucleic acid targets, including the double-stranded genome
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Gene Silencing

In all cells, genetic information that is encoded in DNA is transcribed into RNA, which in turn is translated into protein.

When DNA mutations occur in gene sequences, they are passed on to mutant RNA and, subsequently, to mutant protein. These mutant proteins can be harmful to cells, becoming the cause of many genetic diseases.

Gene silencing is a powerful approach used to address many genetic diseases. Specialized molecules designed to prevent the translation of mutant proteins can bind to and inactivate mutant RNA before it can produce disease-causing proteins, potentially delaying or even preventing genetic disease onset, symptoms or progression.

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Toxic Aggregation

After a DNA mutation is transcribed into RNA, that mutant RNA can form an aggregate together with proteins in the cell

In some diseases, such as myotonic dystrophy type 1, our synthetic medicines can engage with specific regions of a mutant RNA that is responsible for forming RNA=protein aggregates, and release the aggregate. This results in two important disease-resolving events. The first is that the abnormally aggregated proteins which are released can perform their normal functions (which in DM1 involve normal splice function). Secondly and differently from other approaches in the market, we do not degrade the mutant RNA, which is now release from the aggregate, moves to the nucleus, and forms a normal protein which likely resolves certain features of the disease (for example in brain and heart) caused by haploinsufficiency. This is unique to our company and potentially provides better disease relief and potentially eliminates downstream side effects.

PATrOL Platform

NeuBase’s Peptide-nucleic acid Antisense Oligo platform, or PATrOL™ platform, utilizes sequences of engineered peptide-nucleic acids (PNAs). While NeuBase’s PNAs are designed to bind mutant genes and inhibit them from manifesting in disease.

The PATrOL platform yields therapeutics with the broad tissue distribution that is the hallmark of small molecules, while maintaining the highly specific targeting that is characteristic of  traditional genetic medicines.

The Scaffold

Unlike traditional ASOs which have a sugar scaffold, NeuBase’s PNA therapies are designed with a rigid poly-amide scaffold. The synthetic scaffold enables the PATrOL platform to be truly modular and highly scalable, permitting the rapid development of PATrOL-enabled therapies for many different genetic diseases. The scaffold is first-in-class and its neutral charge, resistance to degradation, lack of immunogenicity and semi-rigid nature collectively confer the ability to produce easy to take, precise and well tolerated therapies.

The Nucleobases

NeuBase can develop its PATrOL-enabled therapies using multiple different types of nucleic acid bases, including those that are natural or engineered, allowing for increased selectivity and optimization of the therapy for the target disease. NeuBase is the first and only company to successfully create bifacial Janus bases, engineered bases that target double-stranded DNA or RNA by engaging both strands at once.

The Targeting

NeuBase has developed a proprietary chemistry to decorate its candidates, which allows the therapies to be delivered systemically and achieve broad tissue distribution. We also have programs in place that allow more focused delivery to target tissues when that is an advantage for maximizing efficacy.

The Self-Assembly 

NeuBase chemists have invented a method that gives NeuBase’s PATrOL-enabled drugs the advantages of small molecule therapies. These PATrOL-enabled drugs have proprietary “linkers” on each end, which enable cooperative binding across the gene target. This self-assembly capability confers the ability to address various mutational types such as large expansions and small single-base mutations.

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