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    • 4. 发明申请
    • DESIGN OF SYNTHETIC NUCLEIC ACIDS FOR EXPRESSION OF ENCODED PROTEINS
    • 用于表达编码蛋白的合成核酸的设计
    • US20100029493A1
    • 2010-02-04
    • US12184230
    • 2008-07-31
    • Mark WelchClaes Gustafsson
    • Mark WelchClaes Gustafsson
    • C40B30/02C40B60/12
    • G06F19/24G06F19/20
    • A method of determining a property that affects expression of polynucleotides in an expression system. A plurality of polynucleotides, each encoding a polypeptide sequence, is constructed. An amino acid is encoded a plurality of times in both a first and second polynucleotide in the plurality. The amino acid is encodable by a plurality of synonymous codons including a first codon. The first codon is in the first polynucleotide at a first frequency relative to other synonymous codons, and is in the second polynucleotide at a second frequency relative to other synonymous codons. The first and second frequencies are different. Each polynucleotide is individually expressed in the expression system to measure an expression property value of the polynucleotides, thereby determining a property that affects expression of polynucleotides. The property is an effect that a frequency of use of one or more codons has on expression of polynucleotides in the expression system.
    • 确定影响表达系统中多核苷酸表达的性质的方法。 构建多个编码多肽序列的多核苷酸。 氨基酸在多个第一和第二多核苷酸两者中编码多次。 氨基酸可由包括第一密码子的多个同义密码子编码。 相对于其他同义密码子,第一个密码子以第一个频率位于第一个多核苷酸中,并且相对于其他同义密码子在第二个频率处于第二个多核苷酸。 第一和第二频率是不同的。 每个多核苷酸在表达系统中单独表达以测量多核苷酸的表达特性值,从而确定影响多核苷酸表达的性质。 该性质是一种或多种密码子的使用频率对表达系统中多核苷酸表达的影响。
    • 7. 发明授权
    • Synthetic nucleic acids for expression of encoded proteins
    • 用于表达编码蛋白质的合成核酸
    • US07561972B1
    • 2009-07-14
    • US12184234
    • 2008-07-31
    • Mark WelchClaes Gustafsson
    • Mark WelchClaes Gustafsson
    • G01N33/48C12Q1/00C12Q1/48C07H21/02
    • C12N15/67G06F19/20G06F19/22
    • A method of designing a polynucleotide sequence encoding a polypeptide sequence of a predetermined polypeptide is provided. A frequency lookup table corresponding to an expression system is obtained. The table comprises a plurality of sequence elements and a plurality of frequency ranges, each frequency range for a corresponding sequence element. Each frequency range is a range of frequencies with which a corresponding sequence element can occur in a polynucleotide. The polynucleotide sequence is defined using the frequency lookup table by determining, for each respective sequence element in the frequency lookup table, whether the respective sequence element encodes a portion of the polypeptide sequence. When the respective sequence element encodes a portion of the polypeptide sequence, the sequence element is incorporated into the polynucleotide at a frequency of occurrence that is within the frequency range specified for the respective sequence element in the lookup table. The polynucleotide sequence is then outputted.
    • 提供了设计编码预定多肽的多肽序列的多核苷酸序列的方法。 获得与表达式系统对应的频率查找表。 该表包括多个序列元素和多个频率范围,每个频率范围用于相应的序列元素。 每个频率范围是在多核苷酸中可以发生相应序列元件的频率范围。 使用频率查找表来定义多核苷酸序列,对于频率查找表中的每个相应序列元件,确定各个序列元件是否编码多肽序列的一部分。 当各个序列元件编码多肽序列的一部分时,序列元件以在查找表中对于相应序列元件指定的频率范围内的发生频率被并入多核苷酸。 然后输出多核苷酸序列。
    • 9. 发明授权
    • Systems and methods for constructing frequency lookup tables for expression systems
    • 用于构建表达系统的频率查找表的系统和方法
    • US08401798B2
    • 2013-03-19
    • US12184233
    • 2008-07-31
    • Mark WelchClaes Gustafsson
    • Mark WelchClaes Gustafsson
    • G01N33/34G06F19/00
    • C12Q1/68G06F19/20G06F19/22G06F19/24
    • Methods for determining a property that affects expression of polynucleotides are provided. A plurality of polynucleotides each encoding a polypeptide sequence is constructed. A frequency that a sequence element is used in a first polynucleotide is different than in a second polynucleotide. Each polynucleotide is expressed in an expression system to obtain an expression property value thereby constructing a dataset that contains, for each respective polynucleotide, sequence element occurrence in the respective polynucleotide and the measured expression property value of the respective polynucleotide. A model is computed that describes variation in the measured expression property values as a function of a plurality of variables and weights. From the model, a property that affects expression of polynucleotides in the expression system is determined, where the property is an effect that the frequency of occurrence of one or more sequence elements has on the expression property of polynucleotides in the expression system.
    • 提供了确定影响多核苷酸表达的性质的方法。 构建多个编码多肽序列的多核苷酸。 在第一多核苷酸中使用序列元件的频率与第二多核苷酸不同。 每个多核苷酸在表达系统中表达以获得表达属性值,由此构建对于各个多核苷酸包含各个多核苷酸中的序列元件出现和各个多核苷酸的测量的表达特性值的数据集。 计算描述作为多个变量和权重的函数的测量表达式属性值的变化的模型。 从该模型中,确定影响表达系统中多核苷酸表达的性质,其中性质是一种或多种序列元件的出现频率对表达系统中多核苷酸的表达性质的影响。