Stable RNA Structures promise in drug delivery for cancer treatment

Long non coding RNA is considered as non-protein coding transcripts longer than 200 nucleotides. RNAs are the key regulators of chromatin state and posses more flexible capabilities in building structures than does DNA.

Long non coding RNAs are the key regulatory molecules in the cell and can function well. Many long non coding RNAs are processed to yield small RNAs.  Gametogenesis is essential for sexual reproduction in cells.  Transcription of two long non coding RNAs is used for controling gametogenesis in budding yeast. 

With stable RNA a nanoparticle has been developed that can be used in the  treatment of  cancer and other viral diseases. A long non coding RNA maintains active chromatin and shows surprising results. There are thousands of long non coding RNAs are present in vertebrates animals but only a few of them plays important biological roles. Approximately 30% of the newly identified long non coding RNAs showed littly signal for sequence conservation. And the other 70% were more conserved with Long non coding RNAs sequence processes such as male identity, sperm formation and integration with sperm specific mRNAs.

Biosyn is serving life science community from several years as a reputated drug manufacturing company. We are specialize in manufacturing quality peptide, custom peptide, custom antibody, amino acid analysis, long RNA, oligo synthesis etc.

Viruses are serving the science community from along time and are being used for this purpose. These viruses can be used in the service of science community and plays a very important role in drug delivery by transfering therapeutic genes into body cells to destroy cancer cells. However these genes products can harm the body if they are released at excessive levels. 

Nanoparticles is delivered by RNA which can target cancer genes in mice. The researchers focused on a protein called ID4. The protein ID4 that contributes to embryonic development gets switched off and is reactivated only when ovarian cancer develops. 

Long non-coding RNAs are playing fundamental role in the biological functions of the cells, treatment of cancer and cancer drug delivery and these are expressed in a variety of human cancers.  

The body of all living beings is made up of the basic structural unit called cells which is the basic functional unit of the body. RNA translate the genetic information or signal in the cells of the body. This process is called transcription and RNA plays an important role which necessary for the protein synthesis in cells.

Sometimes by taking some anti cancer drugs or chemicals, this flow of genetic information can be interrupted as it causes any changes in DNA.

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Peptide combinations are more effective in cancer therapy

Studies says that two peptide agents used either together or single with a low-dose of a standard chemotherapy drug results more effective in cancer therapy.

Biosyn.com is a leading quality peptides and other related products manufacturing company. We are dedicated to the service of producing quality peptide and protein research. Peptides are useful in producing collagen, strengthen capillaries and increase micro circulation and increase cellular communication. Peptide improves skin firmness and elasticity and reduces the appearance of wrinkles.

Peptides play a very important role in physiological and biochemical activities of life. We use high technologies and drug manufacturing platform and serving biochemical society for several years. We are specialize in long RNA synthesis, long RNA , bioconjugations, amino acid analysis and other related products and tools.

Two or more amino acids joined in a molecular forms called peptides. The molecules are called peptides, and if the number of amino acids is less than about 50 and the longer molecules are referred to as proteins. Every living cell contains peptides which appear as enzymes, hormones, antibiotics, receptors etc.

Peptides are the great thing in anti-aging skin care. These are utilized in the most skin care products. Peptide improves skin compactness, reduces wrinkles, increases skin tonicity, increases skin firmness.

Peptide combinations delay tumor by inhibiting tumor growth and blocking the formation of new tumor blood vessels. By this way we can reduce the breast cancer and other related diseases. The short amino acid chains the HER2 peptide and VEGF peptide. The HER2 receptor molecule controls the formation of new cells and the VEGF receptor molecule plays an important role in controlling the formation of new blood vessels in tumor.

Research says that vaccinating mice with the HER2 peptide can delay the tumor growth. When this vaccination was combined with VEGF peptide, it delays tumor growth significantly. If we inject the VEGF peptide in animals, we find that tumors did not develop in 40 percent of them. By this way we can say that that VEGF peptide therapy can inhibit the formation of new cell in many cancers.

When we inject the HERF peptide vaccine it causes the immune system to generate antibodies in the body. These antibodies then bind to the over expressed HER2 receptors on caner cells, preventing them from stimulating tumor cells proliferation .

The VEGF peptide binds directly to the VEGF receptor molecules and prevents the formation of new blood vessels.

This combined therapy has not any toxic side effects. Our goal is to develop the best treatment using medicines which are not toxic.

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Prion diseases related peptides

Prion diseases or transmissible spongiformencephalopathies (TSEs) are a family of rare progressive neurodegenerativedisorders that affect both humans and animals. They are distinguished by longincubation periods, characteristic spongiform changes associated with neuronalloss, and a failure to induce inflammatory response.

The causative agents of TSEs are believed to be prions.The term "prions" refers to abnormal, pathogenic agents that aretransmissible and are able to induce abnormal folding of specific normalcellular proteins called prion proteins that are found most abundantly in thebrain. The functions of these normal prion proteins are still not completelyunderstood. The abnormal folding of the prion proteins leads to brain damageand the characteristic signs and symptoms of the disease. Prion diseases areusually rapidly progressive and always fatal.

Familial prion diseases of humans include classicCreutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS),and fatal insomnia (FI). These conditions form a spectrum of diseases withoverlapping signs and symptoms.The prevalent controversial ‘protein-only’ hypothesisproposes that the infectious agent is a misfolded protein that triggers andpropagates the disease in the absence of nucleic acid. The prion protein is thecause for all known mammalian prion diseases. Prion proteins are thought toexist in two different conformations. A properly folded form is denoted PrP^C(for Common or Cellular)and a misfolded form is denoted PrP^Sc (for Scrapie,after one of the diseases first linked to prions and neurodegeneration.) Theprecise structure of the prion is not known but it can be formed by combiningPrP^C, polyadenylic acid, and lipids in a Protein Misfolding CyclicAmplification (PMCA) reaction.

The protein encoded by the major prion protein gene is amembrane glycosylphosphatidylinositol-anchored glycoprotein that tends toaggregate into rod-like structures. The encoded protein contains a highlyunstable region of five tandem octapeptide repeats. This gene is found onchromosome 20, approximately 20 kbp upstream of a gene which encodes abiochemically and structurally similar protein to the one encoded by this gene.Mutations in the repeat region as well as elsewhere in this gene have beenassociated with Creutzfeldt-Jakob disease, fatal familial insomnia,Gerstmann-Straussler disease, Huntington disease-like 1, and kuru. Alternativesplicing results in multiple transcript variants encoding the same protein.

Endotoxin Highlight

Lipopolysaccharides (LPS), commonly known as endotoxin are found in Gram-negative bacteria outer membrane.  Much evidence has shown the ability of LPS in eliciting immune response in human and animalsincluding shock, coagulation, fever and inflammation.  At high concentration, LPS evoke a massive circulation of macrophages and cause major clinical issue in septic shock treatment in human.  Despite the complication that LPS can cause in human, LPS also post a major concern in animal research due to the ability of LPS in inducing immune response. During animal immunization, an antigen is introduced for specific antibody production against the antigen.

  However, the immune response is manifested with the presence of LPS and it often lead to the antibody production against LPS instead of the antigen introduced.  Gram-negative bacteria such as E-coligain much attention in bioengineering and microbiology research. E-coliare best known as the versatile host for protein expression, recombinant protein production and being a vector.  Though, there are many benefits for using E-coliin research, the LPS that are in conjunction could affect the research accuracy and specificity.  For that reason, LPS removal is crucial for all kind of animal research especially when it is related to gram-negative bacteria. 

Bio-Synthesis provides rapid endotoxin detection that is approved.  Despite the endotoxin detection service, we also offer customized endotoxin removal service for our customers.  Our methods offer up to a 90% efficiency of endotoxin removal and with up to 80% protein recovery.

Peptides used in Experimental Encephalomyelitis Models

Encephalomyelitis (EAE), is a widely used animal model for studies of multiple sclerosis. EAE is induced by stimulating T-cell-mediated immunity to myelin antigens. Active induction of EAE is accomplished by immunization with myelin antigens emulsified in adjuvant. The most common EAE models currently studied use rats and mice. Mice are favored because of the abundance of transgenic and targeted gene-deletion models and the numerous antibodies and immunomodulatory reagents available in this species that can be used to dissect the pathogenic mechanisms in EAE.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Even thought all MS patients exhibit signs of neurological deficit, there is considerable variation in the clinical signs and disease course among individuals. The

pathology in the CNS is very heterogeneous, suggesting that MS may be more accurately described as a syndrome arising from multiple pathogenic pathways, rather than a single disease entity. Mechanistic insights into the complex pathogenesis of MS have relied extensively on animal models of CNS demyelination. Although several different models of demyelinating disease in the CNS exist, the most commonly used animal model for MS is EAE. EAE is induced by stimulating an immune response directed against CNS antigens. The origin of the model dates back to 1925 with the discovery that rabbits immunized with human spinal cord homogenate exhibited spinal cord inflammation and paralysis (referred to as active induction). In the 1930s, Rivers et al. showed that EAE could be induced in primates using multiple injections of emulsions of normal rabbit brain tissue. Subsequently, Paterson demonstrated that transfer of lymph node cells from rats immunized with spinal cord homogenate into naïve animals also induced EAE (referred to as passive induction).

Both multiple sclerosis and EAE are considered to be Th1-mediated autoimmune diseases in which neuroantigen-reactive lymphocytes infiltrate the CNS, mediate the development

of inflammatory lesions, and in some models, trigger the demyelination of axons leading to progressive paralysis. Elevated levels of IL-12 have been reported in humans with progressive multiple sclerosis. Increased frequencies of IL-12–secreting monocytes appear to correlate with active brain lesions detected by magnetic resonance imaging. IL-12 has been functionally implicated in the development of EAE by the observations that αIL-12 (αp70) blocks disease development in mice and IL-12 p40–/– mice are resistant to EAE induction.

Active Induction of EAE with PLP and MBP Protein or Peptide

Experimental autoimmune encephalomyelitis (EAE) can be induced in SJL mice by immunization with proteolipid protein (PLP), myelin basic protein (MBP), or peptides. Peptides used correspond to the immunodominant epitopes of MBP (MBP84-104), MOG (MOG92-106), or PLP (PLP139-151 and PLP178-191). In C57BL/6 mice the disease can be induced by immunization with the peptide corresponding to the immunodominant epitope of MOG (MOG35-55).

SJL Mice Info:  Inbr: F104 (J). Albino. Genet: c, p, rd. Origin: Swiss Webster outbred stock from three sources that were brought to The Jackson Laboratory between 1938 and 1943, and pen-bred until 1955, when sib-mating was started. Although the strain has been developed relatively recently, it has rapidly become widely used owing to the high incidence of reticulum cell sarcomas resembling Hodgkin's disease. General biological data on the strain have been reviewed by Crispens (1973). Carries the pink-eyed dilution gene, p, which is derived from Asian mice of the Mus musculus type (see also strains 129/J, P/J and FS/Ei) (Brilliant et al, 1994).

 Source: http://www.informatics.jax.org/external/festing/mouse/docs/SJL.shtml

TABLE 1:      Murine EAE models^a. Encephalitogenic Peptides of MBP, PLP, and MOG in Various Inbred Mouse Strains

Mouse strain	MHC	Peptide	Peptide sequence	Peptide origin	Clinical course
PL/J	H-2u	MBPAc1-11	Ac-ASQKRPSQRHG	rat	Classic
B10.PL	H-2u	MBPAc1-9 PLP178-191 MBP35-47 PLP43-64	Ac-ASQKRPSQR NTWTTCQSIAFPSK TGILDSIGRFFSG EKLIETYFSKNYQDYEYLINVI	rat/mouse mouse rat/mouse mouse	Classic Classic Classic Classic
SJL/J	H-2s	PLP139-151 PLP139-151b PLP178-191 MBP84-104b MBP89-101 MOG92-106d PLP57-70 PLP104-117	HCLGKWLGHPDKF HSLGKWLGHPDKF NTWTTCQSIAFPSK VHFFKNIVTPRTPPPSQGKGR VHFFKNIVTPRTP DEGGYTCFFRDHSYQ YEYLINVIHAFQYV KTTICGKGLSATVT	human/mouse human/mouse mouse rat rat ? mouse mouse mouse	Classicc Classicc Classicc Classicc Classic Classic Classic Classic
C57BL/6	H-2b	MOG35-55 MOG35-55 PLP178-191	MEVGWYRSPFSRVVHLYRNGK MEVGWYRPPFSRVVHLYRNGK NTWTTCQSIAFPSK	rat/mouse human mouse	Classic Classic Classic
NOD	H-2g7	MOG35-55 PLP48-70 PLP56-70	MEVGWYRSPFSRVVHLYRNGK TYFSKNYQDYEYLINIHAFQYV DYEYLINVIHAFQYV	rat/mouse human/mouse	Classic Classic
C3H.SW C3H	H-2b H-2k	MOG35-55 PLP103-116	MEVGWYRSPFSRVVHLYRNGK YKTTICGKGLSATV	rat/mouse	Classic
ABH (Biozzi)	H-2dq1	PLP56-70 MOG8-22	DYEYLINVIHAFQYV PGYPIRALVGDEQED	mouse rat	Classic Classic
A.SW	H-2s	MOG92-106d	DEGGYTCFFRDHSYQ	rat	Atypical
C3H/HeJ	H-2k	PLP190-209 PLP215-232	SKTSASIGSLCADARMYGVL PGKVCGSNLLSICKTAEFQ	human/mouse human/mouse	Classic or Atypical Classic or Atypical
CBA/J	H-2k	PLP190-209 PLP215-232	SKTSASIGSLCADARMYGVL PGKVCGSNLLSICKTAEFQ	human/mouse human/mouse	Atypical Atypical
DBA/1	H-2q	MOG79-96d	GKVALRIONVRFSDHGGY	rat	Classic
BALB/cPt	H-2d	PLP178-191	NTWTTCQSIAFPSK	mouse	na
(SJLX C3H/HeJ)F1	H-2s/k	PLP190-209 PLP215-232	SKTSASIGSLCADARMYGVL PGKVCGSNLLSICKTAEFQ	mouse	na
(SJL X B10.PL) F1	H-2s/q	PLP139-151 PLP178-191 MBPAc1-11	HSLGKWLGHPDKF NTWTTCQSIAFPSK Ac-ASQKRPQRHG	mouse mouse rat/mouse	na
SWR	H-2q	PLP215-232	PGKVCGSNLLSICKTAEF	na	na
(PL/J X SJL) F1	H-2s/u	MBPAc1-11 PLP43-64 PLP139-151	Ac-ASQKRPQRHG EKLIETYFSKNYQDYEYLINVI HSLGKWLGHPDKF	na	na

This table summarizes a variety of murine EAE models that can be actively induced with emphasis on the dominant encephalitogenic epitopes that have been described. This list is not inclusive of all EAE murine models reported in the literature. Strains that are in bold are the most commonly used.

^bMultiple peptides within this region are encephalitogenic.

^cReported to exhibit relapsing-remitting clinical course.

^dPertussis toxin is not required for EAE induction with this strain/antigen combination, but influences the clinical course in A.SW mice.

MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; PLP, proteolipid protein.

Note 1:  The EAE observed in some of these mice is nonclassical. In (SJL X C3H/HeJ)F1 mice, the disease causes imbalance and axial rotary movement (rotary EAE). In BALB/cPt, mice show lack of balance and forelimb paralysis in the absence of hindlimb paralysis.

Note 2:  Sequences for MBP peptides are based on different species variants of MBP, which have different numbering systems; sequences for PLP and MOG peptides are based on the mouse sequence. The reader is urged to consult the indicated references for more detailed information.

References

Burkhard Becher, Brigit G. Durell, and Randolph J. Noelle; Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12 J. Clin. Invest. 110:493–497 (2002).

Brilliant M. H., Ching A., Nakatsu Y., and Eicher E. M. (1994) The original pink-eyed dilution mutation (p) arose in asiatic mice: Implications for the H4 minor histocompatibility antigen, Myod1 regulation and the origin of inbred strains. Genetics 138, 203-211. \par
Crispens C. G. (1973) Some characteristics of strain SJL/JDg mice. Lab. Animal Scie.  23, 408-413. \par

Ingunn M Stromnes & Joan M Goverman; Active induction of experimental allergic encephalomyelitis Nature Protocols 1, 1810 - 1819 (2006)

Stephen D. Miller, William J. Karpus, and Todd Scott Davidson; Experimental Autoimmune Encephalomyelitis in the Mouse Curr Protoc Immunol. 2007 May ; CHAPTER: Unit–15.1. doi:10.1002/0471142735.im1501s77