RNA Aptamer against Autoantibodies Associated with Multiple Sclerosis and Bioluminescent Detection Probe on Its Basis

Vorobjeva, M. A.; Krasitskaya, Vasilisa V.; Фокина, А. А.; Тимошенко, В. В.; Nevinsky, Georgy A.; Venyaminova, Alya G.; Frank, Ludmila A.

doi:10.1021/ac4037894

Cited by 25 publications

(9 citation statements)

References 16 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is believed that MBP and anti-MBP Abs cannot interact with DNA or RNA. However, it was recently shown that anti-MBP IgGs can efficiently interact with nucleic acids [125]. Using quenching of MBP tryptophan fluorescence emission, we have shown that MBP bind oli- In the latter case, it is impossible to exclude possibility of a formation of the chimeric MLChs possessing affinity for MBP and for DNA and also hydrolyzing these absolutely different substrates.…”

Section: Resultsmentioning

confidence: 86%

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Nevinsky¹

2017

Lupus

Self Cite

321

View full text Add to dashboard Cite

Systemic lupus erythematosus (SLE) is known as a systemic polyethiologic diffuse autoimmune disease characterized by connective tissue disorganization and the paramount damage of skin and visceral capillaries. Usually, SLE symptoms include high fever, hair loss, mouth ulcers, chest pain, swollen lymph nodes, painful and swollen joints, increased fatigue, and appearance of red rash more often on the face. The exact reason of SLE appearance is not really clear. Detection of catalytic Abs (abzymes) was shown to be the earliest indicator of different AI disease development. Some abzymes are cytotoxic and can play a dangerous negative role in the pathogenesis of AI diseases. SLE is characterized by the appearance of abzymes with several different catalytic functions including hydrolysis of peptides and proteins, DNA, RNA, and oligosaccharides. In addition, monoclonal SLE abzymes are characterized by extraordinary diversity in the affinity to the substrates, physicochemical and catalytic characteristics, optimal conditions of catalysis, cytotoxicity, etc. Production of abzymes in SLE mice is associated with changes in the differentiation of hematopoietic stem cells of bone marrow, increase in lymphocyte proliferation, and significant suppression of cell apoptosis in different organs. In this chapter, abzymes with different catalytic activities in SLE are described.

show abstract

Section: Resultsmentioning

confidence: 86%

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Nevinsky¹

2017

Lupus

Self Cite

321

View full text Add to dashboard Cite

show abstract

“…Current methods to diagnosis MS require multiple tests and are time consuming. Vorobjeva et al, recently developed an RNA aptamer-based biosensor for the detection of proteolytic autoantibodies against myelin basic protein, the presence of which is a characteristic feature of the disease [59]. A bioluminescent probe was prepared by conjugation of calcium-activated obelin to the RNA aptamer.…”

Section: Targets Relating To Demyelinating Disease and Spinal Cord Inmentioning

confidence: 99%

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

McConnell

Holahan

DeRosa

2014

Nucleic Acid Therapeutics

View full text Add to dashboard Cite

Oligonucleotide aptamers are short, synthetic, single-stranded DNA or RNA able to recognize and bind to a multitude of targets ranging from small molecules to cells. Aptamers have emerged as valuable tools for fundamental research, clinical diagnosis, and therapy. Due to their small size, strong target affinity, lack of immunogenicity, and ease of chemical modification, aptamers are an attractive alternative to other molecular recognition elements, such as antibodies. Although it is a challenging environment, the central nervous system and related molecular targets present an exciting potential area for aptamer research. Aptamers hold promise for targeted drug delivery, diagnostics, and therapeutics. Here we review recent advances in aptamer research for neurotransmitter and neurotoxin targets, demyelinating disease and spinal cord injury, cerebrovascular disorders, pathologies related to protein aggregation (Alzheimer's, Parkinson's, and prions), brain cancer (glioblastomas and gliomas), and regulation of receptor function. Challenges and limitations posed by the blood brain barrier are described. Future perspectives for the application of aptamers to the central nervous system are also discussed.

show abstract

“…It is believed that MBP and anti-MBP Abs cannot interact with DNA or RNA. It was recently shown that anti-MBP Abs efficiently interact with nucleic acids [55]. It should be noted, that MBP is a very hydrophobic protein.…”

Section: Discussionmentioning

confidence: 99%

SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

Timofeeva¹,

Buneva²,

Nevinsky³

2017

Lupus Open Access

View full text Add to dashboard Cite

Objective: DNA-and myelin basic protein (MBP)-hydrolyzing antibodies can play an important role in the pathogenesis of systemic lupus erythematosus (SLE), therefore their analysis seems to be important. Results:In mammalians there are serine proteases, metalloproteases, and DNases. Each of these and many other enzymes catalyze only one chemical reaction. Very unusual and unpredictable situation was revealed by us in the case of monoclonal abzymes corresponding to the sera of patients with SLE. The small pools of phage particles displaying light chains with different affinity for myelin basic protein (MBP) were isolated by affinity chromatography on MBP-Sepharose. In contrast to canonical enzymes, one of twenty five MLChs demonstrated three different enzymatic activities; it efficiently hydrolyzed MBP (but not other proteins) and DNA. Other twenty four MLChs hydrolyzed only MBP. The proteolytic activity of NGTA3-pro-DNase was efficiently inhibited by specific inhibitors of serine-like (PMSF) and metalloproteases (EDTA). Protease and DNase properties of NGTA3-pro-DNase differ significantly from those for the corresponding canonical enzymes.Conclusion: This is the first example of monoclonal antibodies with three different catalytic activities. The principal possibility of the existence of monoclonal antibodies with several different enzymatic activities is unexpected but very important for the further understanding of unknown biological functions of human immunoglobulins.

show abstract

RNA Aptamer against Autoantibodies Associated with Multiple Sclerosis and Bioluminescent Detection Probe on Its Basis

Cited by 25 publications

References 16 publications

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

SLE: Unusual Recombinant Monoclonal Light Chain NGTA3-Pro-DNase Possessing Three Different Activities Trypsin-like, Metalloprotease and DNase

Contact Info

Product

Resources

About