HALO-BIO RNAi THERAPEUTICS
Welcome to Halo-Bio RNAi Therapeutics Inc., an early stage company utilizing the novel 'Multivalent RNAi Platform' to develop multi-gene targeting products for the treatment of disease.
NOVEL RNAi TECHNOLOGIES
The Multivalent RNA molecule (MV-RNA) represent a new RNAi trigger for the treatment of disease. The non-canonical structure utilizes the same RISC pathway as siRNA, but expands gene targeting, eliminates sense-strand off-target effects, and introduces the first 'junction containing' structure to RNAi. With an exlusive IP position and novel technical characteristics, Halo-Bio is working to release Multivalent RNAi based products that utilize MV-RNA's unique capabilities.
EXPERTS IN SINGLE-MOLECULE, MULTI-GENE SUPPRESSION
Multivalent RNA is an elegant single-molecule with advantages in molecular characterization, product cost, and IP ROI. While MV-RNA are more complicated than siRNA given their multivalency, Halo has the expertise and tools to apply MV-RNA to just about any series of target genes.
SOPHISTICATED DESIGN, POWERFUL API, ELEGANT DELIVERY
Halo has spent years developing design support in the form a a powerful computational array called, "Multivalent RNAi Cloud". This enterprise system ensures that products using MV-RNA as the Active Pharmaceutical Ingredient are based on the best possible designs for efficacy and specificity. MV-RNA share the same mechanism of action with canonical siRNA, but they are simply different otherwise. Knowing how to take advantage of this difference is central to Halo being able to provide novel product design, function, and even a new form of RNAi delivery.
PARTNERS & COLLABORATORS
Halo-Bio has relationships with industry-leading researchers in fields relevant to our product developments in Human Therapeutics, BioAgriculture, and Research. As a small company with big ambitions, we always welcome new opportunities and applications for MV-RNA.
Halo-Bio's pending IP provides a unique ROI as it is anticipates Freedom-to-Operate and a greater length of protection than the older canonical dsRNA based IP.
HALO-BIO DATA-TO-DRUG TECHNOLOGIES:1. RNAi CLOUD: Our exclusive MV-RNA design iOS App and computational array.
2. MV-RNA API: Halo's novel RNAi molecule for single-molecule, multi-gene suppression.
3. HALO PARTICLE: A nanoring-like particle composed almost entirely of aptamer directed MV-RNA; truly combining drug with delivery.
HALO-BIO ENABLES ENTERPRISE-CLASS MV-RNAi DESIGN.
Elegantly targeting multiple genes simultaneously in a single MV-RNA molecule is both a scientific and computational challenge. Halo has spent years developing a comprehensive and scalable design platform making sophisticated MV-RNA design easily accessible to all partnering scientists. Introducing "Multivalent RNAi Cloud".
RNAi Cloud provides simplified MV-RNA design with real-time RNA folding, multi-target alignments, organism BLAST, nucleotide editing, RISC-loading energetics, target visualization, and predictive efficacy- all with research grade or GMP manufacturing support.
MULTI-GENE RNAi PROJECTS
RNAi Cloud stores your private projects as well as pre-designed projects targeting pathways in Cancer, Metabolic Diseases, Virus, and more.
"RNAi CLOUD" iOS APP
The complexities of Multivalent RNAi design and project organization is controlled by an easy to use iOS App.
SCALABLE COMPUTATIONAL ARRAY
RNAi Cloud is backed by a fully scalable design providing enterprise-wide access for tens of thousands of researchers. RNAi Cloud can be accessed through Halo-Bio's servers, or through private installations at your institution.
DESIGN: ENTER TARGETS
Want to experiment? Just enter 1-3 genes and let the software figure out the optimal design settings for your targets.
VIEW: PRE-SCREEN COMPUTATIONAL RESULTS
RNAi Cloud design results can contain a surprising number of MV-RNA candidates. Filtering has been built-in to provide reduced screening views for the ideal MV-RNA sequence that meet your interests.
EDIT: TUNE MV-RNA ATTRIBUTES
All MV-RNA identified can be saved and further edited to create the optimum activity priorities. Guide strand length and end composition can be edited and compared to impact on thermodynamics, folding, mis-folding, and targeting in real-time.
SYNTHESIZE: MV-RNA API
Acquiring saved MV-RNA as research quality or GMP quality RNA synthesis is built into RNAi Cloud. Additional support for 'MV-RNA Dicer Modules', 'Targeting MV-RNA Modules', clones in pSUPER or pSUPERIOR vectors is also available when purchasing MV-RNA materials.
EXPLORE THE MV-RNA API
Halo's exclusive Multivalent RNA represent an entirely new class of RNAi triggers capable of simultaneous multi-gene suppression. While these new triggers are similar in activity to canonical siRNA, the MV-RNA's novel targeting, specificity, structural, and IP characteristics make them an ideal Active Pharmaceutical Ingredient (API).
MV-RNA: MULTI-GENE, SINGLE-MOLECULE RNAi
MV-RNA are composed of three RNA guide strands 21-24nt long. Unlike siRNA, which contain a passenger and a guide strand, MV-RNA are composed of 3 guide strands- each aligning to a potential target site.
DICER SUBSTRATE MV-RNA
Single-stranded MV-RNA are designed for applications where a precursor MV-RNA are beneficial to the product use. Uses in Bioagriculture, in-situ production of MV-RNA from a plasmid, or as a HALO PARTICLE module are examples where 'Dicer-Substrate MV-RNA' are advantageous. Single-stranded MV-RNA manufacturing by T7 transcription allows for a cost-effective production of mid and large-scale quantities of MV-RNA.
APTAMER TARGETED MV-RNA MODULE
MV-RNA Precursors with RNA aptamers enable cell-specific targeting of 'Dicer Substrate MV-RNA' either alone or contained with the structure of the HALO PARTICLE.
A LOOK AT SUPPRESSION: ApoB
Converting a known siRNA into a Univalent MV-RNA (one active, two inactive guide strands) results in a repeatable dose dependence with suppressing targets such as ApoB.
IMMUNE STIMULATORY PROFILE: IL-6
MV-RNA are capable of exhibiting a clean IL-6 immunological response without a loss of activity.
Trivalent MV-RNA are designed with all three guides strands targeting suppression at three different sites or targets. These MV-RNA are automatically the default molecule when 3 different genes are entered into RNAi Cloud.
Divalent MV-RNA are designed with two guides strands targeting suppression and one non-targeting strand. These MV-RNA are automatically the default molecule when just one gene is entered into RNAi Cloud as it provides a significant saturation of targeting.
Univalent MV-RNA have only a single active guide strand targeting suppression. Halo uses Univalent MV-RNA in some cases as exploratory siRNA conversions, or controls, but generally relies on Divalent and Trivalent MV-RNA in product development.
MODE OF ACTION
MV-RNA function by RISC catalysis of 1-3 target genes. While this is not surprising, it's important that MV-RNA do not introduce a different mode of action to those used to working with siRNA.
INTELLECTUAL PROPERTY LIFESPAN
Multivalent RNA is the first single-molecule for multi-site RNAi and introduces a new "junction-class' RNAi trigger with expected Freedom-to-operate. Halo's MV-RNA IP is further expected to provide a greater ROI than those of dsRNA or derivative siRNA by providing protection for an additional decade. As the market RNAi therapeutic market grows, the value of this protection is even more significant.
MULTIVALENT SUPPRESSION: ApoB & TTR
Picking a random design targeting both Human ApoB and TTR results in dose dependent suppression of both ApoB and TTR from a single MV-RNA.
*Unscreened, unoptimized MV-RNA as example.
IMMUNE STIMULATORY PROFILE: IL-1b
MV-RNA are capable of exhibiting a clean IL-1b immunological response without a loss of activity.
MV-RNA COMPOSED NANORINGS ARE DRUG & DELIVERY-IN-ONE.
Introducing HALO PARTICLE, our delivery nanoparticle made almost entirely of MV-RNA. Utilizing MV-RNA's exclusive junction as natural RNA architecture, HALO PARTICLE provides a programmable, cell-specific, and potent delivery alternative to commonly used lipid-containing formulations.
SMALL ENOUGH TO PENETRATE
Programmable precise size ranges from 20-100 nanometers, MV-RNA are small enough to accumulate at tumors and sites of inflammation by the EPR effect and could possibly lead to potent treatments for difficult-to-treat diseases.
LARGE ENOUGH TO CIRCULATE
Extending circulation enhances cell-specific targeting. HALO PARTICLES above 20 nanometers help avoid rapid renal clearance.
MV-RNA modules within a HALO PARTICLE contain RNA apatmers designed to bind to certain cell types like Cancer or HBV infected cells. MV-RNA can be programmed to bind to target cells for the therapeutic and avoid non-targeted healthy tissue.
BIOGENESIS OF MV-RNA MODULES
MV-RNA modules are processed by endonucleases in the cell to produce the MV-RNA Complex in-situ. Single-stranded MV-RNA pre-cursor modules exhibit unique characteristics allowing finite nanoarchitectures, thermodynamics, serum stability, and duration of RNAi.
HALO PARTICLES are designed to disassemble at endosomal pH to facilitate release of MV-RNA into the cell for biogenesis and subsequent RNAi activation.
MV-RNA MODULE-> HALO ASSEMBLY
HALO PARTICLE assembly by adding specially designed MV-RNA modules in a step-wise format allowing for the precise construction of the geometry at >95% purity.
HALO PARTICLES composed of MV-RNA modules can be made efficiently at small, mid, or large scales by T7 transcription or synthesis.
A FUTURE OF INNOVATION AWAITS
The MV-RNA as an nanoarchitectural building block allows for future improvements in compaction and alternative geometries that are likely to result in exponential improvements in potency as well as create new therapeutic uses. While already showing promise, MV-RNA particles offer years of innovation opportunities for their clinical use.
Targeted Cancer Therapeutic, 2016
Halo-Bio will soon release details regarding it's first HALO PARTICLE based therapeutic.
Intellectual Property and Licensing.
The growing portfolio consists of at least the following patents and applications related to the MV-RNA RNAi trigger and the delivery of the MV-RNA as a Nanoparticle:
POLYNUCLEOTIDES FOR MULTIVALENT RNA INTERFERENCE, COMPOSTIONS AND METHODS OF USE THEREOF
U.S. Patent No. 9,200,276
Europe, App No. EP 10783959.9
China, App No. 201080034204.7
Japan, Ap No. JP 2012-513363
Canada, Ap No. CA 2,764,158
India, App No. IN 9943/DELNP/2011
POLYNUCLEOTIDES NANOPARTICLES FOR THE MODULATION OF GENE EXPRESSION AND USES THEREOF
62/209,278, Patent Pending
For more information regarding licensing or collaborations, please contact us directly.
How to contact Halo-Bio RNAi Therapeutics
Halo-Bio RNAi Therapeutics, Inc.
Todd M. Hauser
4111 E. Madison, Box 140
Seattle, Washington 98112