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Novel Materials for Viral Purification

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43CA217454-01A1
Agency Tracking Number: R43CA217454
Amount: $224,166.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA16-302
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-01
Award End Date (Contract End Date): 2019-04-30
Small Business Information
5448 PIRE AVE
San Diego, CA 92122-4126
United States
DUNS: 068800915
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 BRADLEY MESSMER
 (858) 455-9976
 messmeb@gmail.com
Business Contact
 BRADLEY MESSMER
Phone: (858) 248-9253
Email: bmessmer@abreosbio.com
Research Institution
N/A
Abstract

Abstract
Viruses have significant commercial application as vectors for gene and cell therapy as well as vaccines for
cancer treatment and infectious diseases The purification of commercial viruses is a major area of bioprocess
development Current methods are mostly based on filtration and chromatography both of which scale poorly
and require clean feed streams to perform well Viral particles are difficult to recover from culture supernatants
or cell lysates because they are similar in size to cell debris A large amount of expensive high quality
nuclease Benzonase is typically needed to reduce the viscosity of the lysate sufficiently for efficient
membrane and column operations Affinity based vector purification has been developed for only one type of
vector some strains of adeno associated virus and is also very expensive In summary virus purification is
challenging and significant amounts of valuable product are lost in inefficient filters
We have developed a novel DNA based avidity reagent termed DeNAno that can provide a significant
advance in the development and manufacturing of commercial viruses with applicability to a variety of viral
vectors DeNAno uses massive avidity rather than affinity to capture biologic targets such as viruses DeNAno
particles are composed of a single stranded DNA concatemer which contains several hundred copies of a
template oligonucleotide The goal of this project is to develop DeNAno particles that bind to a target virus and
then use the DeNAno as a capture reagent for virus purification DeNAno libraries are produced by rolling
circle replication of a circular oligonucleotide template containing a random sequence and specific viral
binders are recovered by a biopanning process DeNAno particles can be released from their targets by
disrupting their secondary structure through divalent cation removal they can also be labeled with nano
particulate magnetite or coated onto micron sized magnetite to allow their use as magnetic capture reagents
We have already performed a selection on adenovirus coated beads and obtained a pool of DeNAno particles
that bind the target virus The specific aims of this project are to characterize DeNAno particles that bind to
the model virus adenovirus and demonstrate their use as a purification tool by attaching them to magnetite
so that they can be used in magnetic capture The virus will be released following capture by divalent cation
removal and the magnetic DeNAno cleared from the viral preparation again by magnet We will assess the
capture efficiency virus yield and infectivity residual DeNAno contamination and the presence of host cell
proteins in the final preparation If successful this project will demonstrate the potential of the DeNAno
technology to streamline virus production and pave the way for additional DeNAno based applications
targeting other commercially important viruses One application of viruses is as a treatment for different diseases including cancer but these viruses are
difficult and expensive to manufacture at sufficient purity This project will develop a new technique that
replaces several cumbersome virus production steps with a simpler and cheaper method of purifying viruses
from their cellular source material

* Information listed above is at the time of submission. *

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