KODE™ technology is the broadest and most simple way to rapidly modify

virtually any biological or non biological surfaces with bioactive

molecules leading to both accelerated R&D and new product possibilities

KODE™ TECHNOLOGY ADVANTAGE If your research or product involves the use of cells, viruses, organisms, bacteria, liposomes, nanoparticles, magnetic beads, solid surfaces or immunoassays then KODE™ biosurface modification technology can probably improve and accelerate your R&D outcomes and enhance your product.

KODE™ constructs can modify almost any biological or non-biological surface with characterized bioactives (including glycans, peptides, proteins, labels, fluorophores, anti-microbials, enzyme-substrates, chelators, etc), within a few minutes, and without affecting cell/virion/organisms vitality and functionality. KODE™ constructs can also modify solid surfaces including papers, nanofibres, filter membranes, plastic, rubbers, glass and metal in a just few seconds, with a water-resistant bioactive coating.

Additionally KODE™ technology can allow you to real-time image, adhere, and separate modified cells / virions both in vitro and/or in vivo. It can also improve solubility, enable in vivo targeting, cause antigen masking, enhance or suppress bioactivity, improve in vivo half life, modify surface charge, improve functionality and visibility, neutralize antibodies and toxins, and inhibit infection (viral and microbial) and much more.

Simply add additional features to current procedures, as KODE™ modification is additive and generally concurrently compatible with almost all existing technologies.

Select from a library of KODE™ R&D constructs or contact us to design and synthesize your own designer construct.

FURTHER INFORMATION

Steve Henry CEO/CSO, KODE Biotech shenry@kodebiotech.com

www.linkedin.com/in/kodebiotech www.kodebiotech.com www.kodecyte.com http://www.jove.com/details.php?id=3289 Internet search term “kodecyte”

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BIOLOGICAL MODIFICATION OF SURFACES All natural biological surfaces (e.g. cells, viruses, microbes and organisms) exhibit a large range of complex biological molecules with functions ranging from structural integrity and basic biological processes to being key modulators of biological recognition, communication, cell-to-cell interaction and other functions such as immune response, infection, inflammation, and apoptosis, etc.

The ability to precisely control, manipulate and mimic biological surfaces, and alter their properties is potentially one of the most important areas in biotechnology. Modified natural and/or synthetic biosurfaces have applications in diagnostics, biotherapeutics, tissue engineering, transplantation, immunology, oncology, drug targeting and release, biosensors, bioelectronics and research & development.

KODE™ functional-spacer-lipid (FSL) constructs offer unparalleled flexibility for mimicking biosurface components and

attaching one or more novel function(s) to intact biological and synthetic surfaces alike.

FUNCTION SPACER LIPID CONSTRUCTS

KODE™ Technology is based on FSL constructs which consist of three components; a functional head group (hydrophilic) a spacer and a lipid tail (hydrophobic). Each of the components of the FSL construct can be engineered. The functional head group is usually the bioactive component of the construct with the various spacers and lipids tails influencing and effecting its presentation, orientation, location and adhesion to surfaces.

Central to all FSL constructs is the requirement to be dispersible in water.

The functional head can be almost anything, but typically needs to be hydrophilic.

The functional head of an FSL usually has <100 sugars residues or <60 amino acids because if the functional head group becomes too large it has the potential to disrupt the insertion process. If a large functional head is required, then it can be secondarily acquired after surface

modification by a smaller primary FSL

such as FSL-biotin (via an avidin-biotin bridge) or an FSL-chelator, FSL-enzyme substrates, FSL-click-chemistry, FSL-reactive functional group (eg maleimide) or FSL-antigen, etc

The spacer is an integral part of the FSL construct and gives it several important characteristics including water dispersibility.

A variety of different spacers exist (which can also be functionalized to provide a larger

range of functions). Specific feature of spacers include: Variable length - the ability to vary the length of the spacer, for example 1.9nm (Ad), 7.2nm (CMG2), 11.5nm (CMG4), allowing for enhanced presentation of functional groups at the biosurface.

Optimizes presentation of bioactives (F). The presentation of the bioactive on a spacer reduces steric hindrance and increases bioactive surface exposure and availability for interaction – this increases sensitivity and specificity thereby improving signal to noise ratios

Rigidity - the spacers used are generally relatively rigid although alternative spacers are available that are flexible

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Substitutions – CMG spacers can be internally modified and functionalized to bring about additional features.

Branches – usually the spacer is linear, but it can also be branched including specific spacing of the branches to optimize presentation and biological interaction of the functional head group.

Inert – important to the design of FSL constructs is the biologically inert nature of

the spacer.

This feature means the Spacer-Lipid components of the constructs are unreactive with undiluted serum. Consequently the constructs are compatible in vivo and can improve diagnostic assay sensitivity by allowing for the use of undiluted serum. Attempts to stimulate an immune response to the S-L components of the FSL so far have been unsuccessful – indicating at least they are poorly immunogenic.

In the figure below is shown the two common forms of spacers used to make FSL constructs. The left most FSL construct has the functional head group conjugated via an O(CH2)3NH spacer to an activated adipate while the three constructs in the centre have partially carboxymethylated oligoglycine (CMG2) spacers. The final trimeric headed FSL is also based on CMG2 but in this construct a tetrameric CMG2 construct was used for construction, with a lipid attached to one-arm and three identical functional groups to the remaining three arms. Such multimeric headed FSL spacers have improved sensitivity and biologic activity.

In addition to the ability to modify both the functional biohead and the spacers, the lipid tail can also be modified to bring about specific biological effects. The most commonly used lipid on an FSL construct is 1,2-dioleoyl-sn-glycero-3-phospho ethanolamine (DOPE) however sterols (δ-oxycarbonyl aminovaleric acid derivative of cholesterol) and ceramides can also be used.

It is important to note that the lipid tail is not necessarily an anchor, but it instead imparts an amphiphatic character to the

construct, and this causes the construct to spontaneously self-assemble on surfaces.

KODE™ TERMINOLOGY To facilitate description of FSL construct modified surfaces to be accurately described, a series of KODE™ Technology related terms have been adopted. These include:

• KODE™ Technology – a platform of water dispersible, function-spacer-lipid constructs, which when contacted with a surface will self-assemble to create a water resistant coating

• FSL or function-spacer-lipid construct – a generic description of a construct consisting of a functional component, a spacer and a lipid that meets the criteria defined by KODE™ Technology

• FfSL – an FSL with a functionalized spacer (and a functional head)

• FSdL, FSsL, FScL – terms used when using FSL constructs with different lipid tails. The lipid tails are identified as dL (DOPE), sL (sterol) and cL (ceramide)

• kodecyte – a cell modified by KODE™ Technology • kodevirion – a virion modified by KODE™

Technology • kodesome – a liposome modified by KODE™

Technology • koderia – a bacteria modified by KODE™

Technology • koding – the process of FSL modification of a

surface • koded – the result of koding

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FSL SURFACE COATING Many bioactive components are difficult or impossible to attach to biological or synthetic surfaces, and even if they do attach, their presentation is often random.

In contrast, the attachment of an FSL construct to a solid membrane or surface

relies primarily not upon the features of the bioactive component but instead upon the amphipathic and self-assembling nature of

spacer-lipid of the FSL construct.

The presence of the spacer in the construct also improves and controls the presentation of the bioactive at a biological or non-biological surface. When FSL constructs are present in a solution they may form simple micelles or adopt more complex bi/multi layer structures the longer they remain in solution (they will also form a coating on the surface of the container they are in and this may also start to multi-layer with storage). We therefore recommend that solutions of FSLs should be sonicated for up to 1 minute if stored in solution to disrupt complex structures as these may show different membrane insertion dynamics. The nature of FSL micelles will be determined in part by the combination of functional group, spacer and lipid together with temperature, concentration, size and hydrophobicity / hydrophilicity for each FSL construct.

Because FSL constructs have a preference for free lipids, solutions for diluting FSLs and surfaces to be labeled should be free of lipids (and detergents) or use very high FSL concentrations (usually 40× higher). After labeling the constructs will be present and orientated at the membrane surface and will not be easily removed by water, PBS, serum, detergents or other biological compatible fluids.

The expected mechanism of labeling cells/liposomes or surfaces with a lipid membrane is via insertion of the FSLs lipid tail into the lipid membrane. Labeling of lipid membranes takes significantly longer to label (up to an hour) than non-lipid surfaces (which usually take only a few seconds – minutes).

It is expected that the FSL will be highly mobile within the membrane and the choice of lipid tail may effect is relative partitioning within the membrane. The construct unless it has flip-flop sequences is expected to remain only surface presented.

FSL modification is not permanent in living cells and constructs will be lost from the

surface by several mechanisms. Firstly FSLs will be lost by endocytosis along with other membrane components, secondly they may be diluted if the membrane expands or divides (as in cell division), and thirdly when present in vivo with serum lipids FSLs will slowly exchange into the plasma at a rate of about 1% per hour (but not reinsert into other cells). The in vitro rate of loss is generally proportional to the activity of the membrane and division rate of the cell (with dead cells remaining highly labeled). Additionally fixed cells or inactive cells (e.g. red cells) stored in serum free media will retain constant high levels of the FSL constructs. Inserted fluorophores may also undergo enhancement during storage as a consequence of dequenching due to distribution of FSL constructs over time (as seen in viruses – see FAQs).

Liposomes are easy koded by simply adding FSL constructs into the preparation. Contacting kodesomes with microplates or other surfaces can cause the direct labeling of the surface.

The labeling of non-lipid surface will occur via multiple mechanisms, but all are driven primarily by the need to “exclude water”.

It is expected that direct binding of the lipid of the FSL will occur with hydrophobic surfaces, similar to lipid membranes but without the ability to insert. Mechanisms of binding onto other surface are more complex.

Because the constructs are able to bind to virtually any surface, be it hydrophobic or hydrophilic the mechanisms of action are

multiple and complex and include hydrophobic interactions (via lipid tail),

hydrophilic interactions (via head group and spacer), micelle entrapment, encapsulation,

bi/multi layer assembly, and other factors such as hydrogen bonding, van der Waals

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forces, electrostatic and ionic interactions and combinations of all the above on

complex surfaces.

On complex surfaces such as intact bacteria potentially all mechanisms may be contributing to creating a surface coating. However despite the potential variety of mechanism at play, the method of coating and outcomes are usually the same independent of the type of surface. A note of caution is that the detection methods used to observe the FSL coating may be affected by the type of surface – for example enzyme precipitates may not adhere despite presence of a significant FSL layer.

Image shows koderia (koded bacteria) adhered to a koded microsphere

It should be noted that once the first layer of FSL has adhered to the surface, the koded surface it can start to form multiple layers of FSL upon itself (particularly if FSL concentrations used are high). These additional layers may show different performance characteristics than the primary adhered FSL layer and so experimentation should be undertaken to establish this.

The only surfaces so far encountered that are unlabeled with FSL constructs appear to be the β-glycans of yeast.

It appears that yeast will only label on their chitin rings (hydrophobic) and not elsewhere. Further investigations are underway to determine the mechanisms involved and the extent to which other organisms/materials can’t label.

PREPARATION OF KODED SURFACES If the surface to be modified is a particles simply mix 1 part of cells/virions/particles/bacterium (in lipid free media) with one part of an FSL solution (containing 1 or more FSLs) and incubate for 10-120 minutes for cells at 37°C (or longer at temperatures as low as 4°C) or 1-120 seconds for surfaces. If the surface is a large solid then apply the FSL by immersion, flooding, painting, spraying or inkjet printing.

In all methods the constructs will spontaneously incorporate into the

membrane or self-assemble onto the surface and no further steps are required.

The construct does not have to dry in order to form a coat on a surface. Typical FSL concentration range is between 20-100 µg/mL although solution with concentrations as low as 1µg/mL are used in some applications. If very high concentrations are used the constructs may start to multilayer on the surface (which is sometimes a desirable feature). Experimentation is recommended to establish the optimal concentration and time for different surfaces.

Kodecytes can also be created in vivo by injection of large amounts of FSL constructs directly into the circulation. However this process will modify all cells in contact with the constructs and usually require significantly more (40×) construct than in vitro preparation, as FSL constructs will preferentially associate with free lipids.

FSL INKJET PRINTING

All FSL constructs disperse in water and are therefore compatible with inkjet printers (either thermal or piezo). FSL constructs can be printed with a standard desktop inkjet printer directly onto paper to create immunoassays. An empty ink cartridge is filled with an FSL construct and words,

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barcodes, or graphics are printed. An acrylic template is adhered to the surface to create reaction wells.

The method is then a standard EIA procedure, but blocking of serum is sometimes not required and undiluted serum can be used (this will depend on the type of surface being used). A typical procedure is as follows: print and assemble plates (stable once printed for years), add serum, incubate 30-60 min, wash by immersion in PBS, add secondary EIA conjugate, incubate (30 min), wash, add NBT/BCIP precipitating substrate (5 min) and stop the reaction when developed by washing. The developed result is stable for years. If the surface to be printed on is metal, glass, etc then it is important to establish that the precipitating substrate created by enzyme is able to bind to the surface or an alternative visualization method is required.

Image above is a typical example of an inkjet printed EIA where 11 different FSL glycan constructs were printed as identifying codes on paper and then reacted against different samples. The activity of the antibody in the samples can be identified by appearance of words identifying the target antigens it reacts against.

APPLICATIONS/PRODUCTS There are a large variety of proven applications and products using KODE™ technology. Readers are referred to the articles listed in the references and specific result examples shown in the FAQ section.

Generally speaking, FSLs can be applied in almost all areas of biotechnology.

R&D tools – a full toolbox

glycosylation antigen addition animal modeling interactions masking targeting anchoring recovery imaging

anti-microbials tracking antibodies cell separation inhibition labels neutralization bioassays immobilization

nanoparticles bacteria viruses controls microfluidics biosensors

viability assays environmental bioprinting

Diagnostics – rapid and sensitive diagnostic assays can be created on almost any surface ranging from solids such as membranes, glass, silicon wafers, metals etc through to magnetic beds or cells which can carry the diagnostic antigen/antibodies on there surface. Cells, proteins and antibodies can be anchored or captured on koded surfaces.

Therapeutics – although no therapeutic product is as yet on the market KODE™ technology is being evaluated in a variety of product/R&D pipelines. These include …

inhibition neutralisation animal modeling viruses toxins antibodies adjuvants stem cells immunogens

liposomes masking drug delivery tolerance cell therapy targeting

oncology complement lubricants radio-isotopes wound-care opthalmology

respiratory anti-microbial imaging implants fertility nanofibres

Industrial

In addition KODE constructs are under-evaluation as anti-counterfeiting measures (including labeling of cells and viruses), cosmetics, and for creating anti-bacterial surfaces.

KEY TECHNOLOGY FEATURES The technological features of KODE™ FSL constructs and the koding process can be summarized as follows:

(1) EASY: Simplest and most rapid biosurface engineering technology available today – just add one or more FSLs to a solution then contact it with cells/viruses/bacteria/particles/

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surfaces and it is ready to use within an 1 hour

(2) CUSTOMIZABLE: variable design of the KODE™ Construct allows for optimization of function.

(3) AVAILABLE: Off-the-shelf KODE™ R&D constructs are currently available from KODE Biotech Materials and Sigma-Aldrich. Custom designed construct service is also available (upon request)

(4) PROVEN: Established and validated technology – published peer-reviewed journals articles and several commercial products in the market

(5) RELIABLE: Robust and replicable process – same methodology for all constructs and same results every time

(6) CONTROLLABLE: simply change FSL concentrations to create an extensive ranges of quantitative variants, including calibration curves

(7) ADDITIVE: build upon your existing platforms by adding additional features and functions

(8) ENHANCING: allows for increased sensitivity and specificity, optimization of reactivity and biomarker presentation

(9) VERSATILE: same construct can be used on various biological and synthetic surfaces (e.g. cells, viruses, paper, microspheres) expanding experimental options

(10) SAFE: no additional handling precautions are required for modified cells/viruses and there is no known toxic profile

(11) BENIGN: koding does not impair normal biological functions (other than to introduce a new function/effect) – non-genetic, non-covalent, gentle process involving no solvents, detergents or harsh chemicals

(12) ENABLING: Facilitates attachment of non-binding molecules to surfaces or alternatively can enable attachment of molecules to normally non-binding surfaces

(13) COMPATIBLE: suitable for use in all biological systems including in vivo

(14) BROAD: Broadest application range of any competing technology, allowing modification of almost any biological and synthetic surfaces with almost any bioactive

(a) Cells (e.g. blood cells, cultures, sperm, embryos) (b) Viruses (e.g. influenza, measles, varicella) (c) Organisms (e.g parasite, zebrafish) (d) Bacteria (e.g coccus & bacillus) (e) Vesicles (e.g. liposomes, micelles and lipids) (f) Surfaces (e.g. hydrophobic/hydrophilic membranes,

fibres, microspheres, magnetci beads, paper, nitrocellulose, silica, glass, cotton, etc)

(g) Solutions (e.g saline, plasma/serum, culture media)

KODE™ CONSTRUCT SUPPLY

Sigma-Aldrich and KODE Biotech Materials both offer a limited range of FSL constructs for R&D use. Constructs can be custom built where required.

Authorized KODE™ Construct Manufactures and Suppliers are able to supply constructs to required quality standards including for therapeutic use.

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KODE BIOTECH

KODE Biotech Ltd and its US-based licensing partner Emergent Technologies licenses KODE™ technology to commercial and academic partners for both R&D and product development.

http://www.emergenttechnologies.com

KODE™ TECHNOLOGY REFERENCES

KODE Biotech and Emergent have established track records in working with partners including big Pharma, and bringing step-change products to successful market outcomes.

KODE Biotech’s licensing and collaborative partnering focuses on supporting licensees to gain market advantages by leveraging KODE™ technology.

For further information contact either KODE Biotech or Emergent and we will be happy to discuss you commercialization opportunities using KODE™ Technology

Journal  reference   Short  Synopsis  Perry H, Henry S. Training students in serologic reaction grading increased perceptions of self-efficacy and ability to recognise serologic reactions but decreased grading accuracy. Transfusion (in press 2015)

Kodecytes are able to assist in training students to recognize serologic reactions

Ilyushina NA, Chernyy ES, Korchagina EY, Gambaryan AS, Henry SM, Bovin NV. Labeling of influenza viruses with synthetic fluorescent and biotin-labeled lipids. Virologica Sinica 2014, 29 (4): 199-210 DOI 10.1007/s12250-014-3475-1

Limitation of using FSL-FLRO4 are examined on influenza virus

Barr K, Kannan B, Korchagina E, Popova I, Ryzhov I, Henry S, Bovin N. Biofunctionalizing nanofibres with carbohydrate blood group antigens. Beilstein (under review)

FSL constructs were applied to nanofibres both after and during manufacture

Barr K, Korchagina E, Popova I, Bovin N, Henry S. Monoclonal anti-A activity against the FORS1 (Forssman) antigen. Transfusion (in press) doi: 10.1111/trf.12773

Kodecytes and printed FSLs allow for the detection of monoclonal reagent activity against the FORS1 antigen

Katie Barr, Elena Korchagina, Ivan Ryzhov, Nicolai Bovin, and Stephen Henry. Mapping the fine specificity of ABO monoclonal reagents with A and B type-specific function-spacer-lipid constructs in kodecytes and inkjet printed on paper. Transfusion 2014;54: 2477-84 DOI 10.1111/trf.12661

Kodecytes and printed FSLs allow for the detection of the specificity of monoclonal reagent activity

Tesfay MZ, Krik A, Hadac EM, Griesmann GE, Federspiel MJ, Barber GN, Henry SM, Peng K-W, Russell SJ. PEGylation of vesicular stomatitis virus extends virus persistence in blood circulation of passively immunized mice. J Virology 2013; 87: 3752-3759 DOI: 10.1128/JVI.02832-12

Mayo Clinic used FSL-PEG constructs to extend the circulatory life of virus

Svensson L, Hult AK, Stamps R, Angstršm J, Teneberg S, Jorgensen R, Rydberg L, Henry SM, Olsson ML. Forssman expression on human erythrocytes: Biochemical and genetic evidence of a new histo-blood group system. Blood 2013; 121: 1459-1468. DOI 10.1182/blood-2012-10-455055

FSL constructs were used to add back to red cells missing E coli receptors

Henry S, Barr K, Oliver C. Modeling transfusion reactions with kodecytes and enabling ABO-incompatible transfusion with Function-Spacer-Lipid constructs. ISBT Science Series 2012; 7: 106-111 doi: 10.1111/j.1751-2824.2012.01563.x

Review on use of FSLs to neutralise circulating ABO antibodies and allow incompatible transfusion (in mouse model). Also shows inkjet printing antibody assay.

Korchagina E, Tuzikov A, Formanovsky A, Popova I, Henry S, and Bovin N. Toward creating cell membrane glycolandscapes with glycan lipid constructs. Carbohydrate Research 2012; 356: 238-246 http://dx.doi.org/10.1016/j.carres.2012.03.044

Review of synthesis of FSL constructs and most applications related to sugars

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Lan C-C, Blake D, Henry S, Love DR. Fluorescent Function-Spacer-Lipid construct labelling allows for real-time in vivo imaging of cell migration and behaviour in zebrafish (Danio rerio) Journal of Fluorescence 2012; 22: 1055-1063 doi 10.1007/s10895-012-1043-3

In vivo bioimaging using FSL constructs and real-time cell tracking - in zebrafish

Lan C-C, Blake D, Henry S, Love DR. Videos relating to Fluorescent Function-Spacer-Lipid construct labelling allows for real-time in vivo imaging of cell migration and behaviour in zebrafish (Danio rerio) 2012; http://hdl.handle.net/10292/3475

Videos of kodecytes in the circulation

Harrison AL, Henry S, Mahfoud R, Manis A, Albertini A, Gaudin Y, Lingwood CA, and Branch DR. A novel VSV/HIV pseudotype approach for the study of HIV microbicides without requirement for level 3 biocontainment . Future Virology 2011; 6(10): 1241-1259 doi: 10.2217/fvl.11.88

Toronto University show prevention of HIV infection of cells with FSL-GB3

Hult AK, Frame T, Chesla S, Henry S, Olsson ML. Flow cytometry evaluation of red blood cells mimicking naturally-occurring ABO subgroups following modification with variable amounts of FSL-A and B constructs. Transfusion 2012; 52: 247-251 doi: 10.1111/j.1537-2995.2011.03268.x

Flow cytometry of kodecytes made to mimic antigen strengths of ABO cells with weak antigen expression

Blake DA, Bovin NV, Bess D, Henry SM. FSL Constructs: A simple method for modifying cell/virion surfaces with a range of biological markers without affecting their viability. J Visualized Experiments 2011 Aug 5;(54). e3289 doi: 10.3791/3289 (http://www.jove.com/details.php?id=3289).

Video and protocol showing generic use of KODE technology - sponsored by Sigma-Aldrich

Georgakopoulos T, Komarraju S, Henry S, Bertolini J. An improved Fc function assay utilising CMV antigen coated red blood cells generated with synthetic Function-Spacer-Lipid constructs. Vox Sanguinis 2012; 102: 72-78 DOI: 10.1111/j.1423-0410.2011.01512.x

FSL-CMV peptides were used to create an assay for determining Fc functionality of IgG prepared for in intravenous infusion

Henry SM, Komarraju S, Heathcote D, Rodinov I. Designing peptide-based FSL constructs to create Miltenberger kodecytes. ISBT Science Series 2011; 6: 306-312 DOI: 10.1111/j.1751-2824.2011.01505.x

Review of the principles for making peptide based-FSL constructs

Hadac EM, Federspiel MJ, Chernyy E, Tuzikov A, Korchagina E, Bovin NV, Russell S, Henry SM. Fluorescein and radiolabeled Function-Spacer-Lipid constructs allow for simple in vitro and in vivo bioimaging of enveloped virions J Virological Methods 2011;176:78-84 doi:10.1016/j.jviromet.2011.06.005

Mayo Clinic shows FSL-fluoroscent and FSL-radiolabeling of virus and bioimaging of labled virus in mice

Oliver C, Blake D, Henry S. In vivo neutralization of anti-A and successful transfusion of A antigen incompatible red cells in an animal model. Transfusion 2011; 51: 2664-2675 doi: 10.1111/j.1537-2995.2011.03184.x

Circulating antibodies were neutralised with FSLs allowing for incompatible transfusion - in mice

Oliver C, Blake D, Henry S. Modeling transfusion reactions and predicting in vivo cell survival with kodecytes. Transfusion 2011; 51: 1723-1730 doi: 10.1111/j.1537-2995.2010.03034.x

FSL biotin labeled red cells can be used to determine in vivo cell survival and allow for retrieval of cells from the circulation

Harrison, AL, Olsson ML, Brad Jones R, Ramkumar S, Sakac D, Binnington B, Henry S, Lingwood CA, Branch DR. A synthetic globotriaosylceramide analogue inhibits HIV-1 infection in vitro by two mechanisms. Glycobiology 2010;27:515-524 doi 10.1007/s10719-010-9297-y

Toronto University shows Inhibition of HIV virus infection with FSL-GB3

Heathcote D, Carroll T, Wang JJ, Flower R, Rodionov I, Tuzikov A, Bovin N & Henry S. Novel antibody screening cells, MUT+Mur kodecytes, created by attaching peptides onto erythrocytes. Transfusion 2010;50:635-641 doi: 10.1111/j.1537-2995.2009.02480.x

Asian blood group antigens (FSL-peptides) used to create diagnostic assay

Henry S. Modification of red blood cells for laboratory quality control use. Current Opinion in Hematology 2009; 16(6):467-472 DOI:10.1097/MOH.0b013e328331257e

Review of the use of kodecytes as QC cells. First use of term kodecyte.

Frame T, Carroll T, Korchagina E, Bovin N, Henry S. Synthetic glycolipid modification of red blood cell membranes. Transfusion 2007; 47: 876-882 doi: 10.1111/j.1537-2995.2007.01204.x

FSLs (SYNs) used to create ABO ,Lewis modified red cells

V. S. Nadarajan, A. A. Laing, S. M. Saad & M. Usin. Prevalence and specificity of red-blood-cell antibodies in a multiethnic South and East Asian patient population and influence of using novel MUT+Mur+ kodecytes on its detection Vox Sang. 2012 Jan;102(1):65-71. doi: 10.1111/j.1423-0410.2011.01507.x

Independent validation of KODE Miltenberger product

For further information please also view our other information document

FREQUENTLY ASKED QUESTIONS ABOUT KODE™ SURFACE MODIFICATION TECHNOLOGY