Multivalent RNAi

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.

LICENSING:

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".

DESIGN-TO-DRUG SCREENING

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.RNAi Cloud Computational Array

DESIGN: ENTER TARGETS

Want to experiment? Just enter 1-3 genes and let the software figure out the optimal design settings for your targets.

RNAi Cloud iPhone

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 / siRNA Comparison

MV-RNA COMPLEX

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.

The MV-RNA Complex

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.

Dicer Substrate 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.

Aptamer Targeting MV-RNA



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.

ApoB Suppression

IMMUNE STIMULATORY PROFILE: IL-6

MV-RNA are capable of exhibiting a clean IL-6 immunological response without a loss of activity.

IL-6 Response

TRIVALENT MV-RNA

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.

Trivalent MV-RNA

DIVALENT MV-RNA

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.

Divalent MV-RNA

UNIVALENT MV-RNA

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.

Univalent MV-RNA

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 represent a new class of 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.

ApoB / TTR Suppression*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.

IL-1 Response

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

At 30-40 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.

PROGRAMMABLE TARGETING

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.

ENDOSOMAL STOICHIOMETRY

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.

SCALABILITY

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, 2014

Halo-Bio will soon release details regarding it's first HALO PARTICLE based therapeutic.

Intellectual Property and Licensing.

Halo Bio owns national and international pending patents.

Multivalent RNA

(PATENT PENDING)

Multivalent RNA is the first single-molecule for multi-site RNAi.

Controlled Biogenesis of RNA Interference

(PATENT PENDING)

Nanoparticle building blocks with cell specificity and non-invasive degradability.

endoGUIDE RNA

(PATENT PENDING)

The endoGUIDE RNA provides a new mechanism for gene silencing in bacteria and humans against coding or non-coding genes.

Asymmetric shRNA/siRNA Precursors

(PATENT PENDING)

A-shRNA replaces shRNA with a novel RNA precursor that is more specific and pathway independent.

For more information regarding licensing or collaborations, please contact us directly.

Contact Halo-Bio.

How to contact Halo-Bio RNAi Therapeutics

Halo-Bio RNAi Therapeutics, Inc.

Todd M. Hauser
thauser@halo-bio.com

Halo-Bio Research Products Division: Oligoengine

1-800-755-1620 (U.S. and Canada)

Fax Number

1-(206)-254-0300

Mailing Address

4111 E. Madison, Box 140
Seattle, Washington 98112

 

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